System and method for a biosensor monitoring and tracking band

ABSTRACT

A health care band operably attaches a biosensor to a patient. The biosensor includes one or more sensors for collecting vitals of a patient and a wireless transmitter that is configured to communicate with an EMR network that stores and maintains an EMR of the patient. The biosensor stores a unique identification associated with the patient&#39;s EMR such that vitals measured by the biosensor may be transmitted with the patient&#39;s unique identification for storage in the patient&#39;s EMR. The sensors in the biosensor may include a temperature sensor and motion detector/accelerometer. In an embodiment, one of the sensors includes a photoplethysmography (PPG) based sensor configured to continuously or periodically measure a patient&#39;s vitals, such as heart rate, pulse, blood oxygen levels, NO concentration levels, or other blood analytics.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims priority under 35 U.S.C. § 120 as acontinuation application to U.S. application Ser. No. 15/275,444,entitled “System and Method for a Biosensor Monitoring and TrackingBand,” filed Sep. 25, 2016, and hereby expressly incorporated byreference herein.

U.S. application Ser. No. 15/275,444 claims priority as a continuationin part under 35 U.S.C. § 120 to U.S. Utility application Ser. No.14/866,500 entitled, “System and Method for Glucose Monitoring,” filedSep. 25, 2015, and hereby expressly incorporated by reference herein.

U.S. application Ser. No. 15/275,444 claims priority under 35 U.S.C. §119 to U.S. Provisional Application No. 62/194,264 entitled, “System andMethod for Glucose Monitoring,” filed Jul. 19, 2015, and herebyexpressly incorporated by reference herein.

U.S. application Ser. No. 15/275,444 claims priority under 35 U.S.C. §119 to U.S. Provisional Application No. 62/276,934 entitled, “System andMethod for Health Monitoring including a Remote Device,” filed Jan. 10,2016, and hereby expressly incorporated by reference herein.

U.S. application Ser. No. 15/275,444 claims priority under 35 U.S.C. §119 to U.S. Provisional Application No. 62/307,375 entitled, “System andMethod for Health Monitoring using a Non-Invasive, Multi-Band Sensor,”filed Mar. 11, 2016, and hereby expressly incorporated by referenceherein.

U.S. application Ser. No. 15/275,444 claims priority under 35 U.S.C. §119 to U.S. Provisional Application No. 62/312,614 entitled, “System andMethod for Determining Biosensor Data using a Broad Spectrum LightSource,” filed Mar. 24, 2016, and hereby expressly incorporated byreference herein.

U.S. application Ser. No. 15/275,444 claims priority under 35 U.S.C. §119 to U.S. Provisional Application No. 62/373,283 entitled, “System andMethod for a Biosensor Monitoring and Tracking Band,” filed Aug. 10,2016, and hereby expressly incorporated by reference herein.

U.S. application Ser. No. 15/275,444 claims priority under 35 U.S.C. §119 to U.S. Provisional Application No. 62/383,313 entitled, “System andMethod for a Drug Delivery and Biosensor Patch,” filed Sep. 2, 2016, andhereby expressly incorporated by reference herein.

U.S. application Ser. No. 15/275,444 claims priority as a continuationin part under 35 U.S.C. § 120 to U.S. Utility application Ser. No.15/275,388 entitled, “System And Method For Health Monitoring Using ANon-Invasive, Multi-Band Biosensor,” filed Sep. 24, 2016, and herebyexpressly incorporated by reference herein.

FIELD

This application relates to a systems and methods of non-invasive,autonomous health monitoring band, and in particular a health monitoringband that assists in tracking patient's medical records for use in anelectronic medical record system and network.

BACKGROUND

Tracking of a patient's admission, medical records, and/oradministration of medicine and treatments to the patient in a hospitalor other healthcare facility currently includes use of a barcode on anarmband of the patient. The bar code on the patient's armband must bescanned with a physical scanner to identify the patient prior toadministering the medicine, recording vitals, performing procedures,etc.

In addition, the patient's vitals, such as temperature, blood oxygenlevels, blood pressure, etc., must be monitored periodically typicallyusing one or more additional instruments. For example, additionalinstruments for obtaining vitals of a patient include blood pressurecuffs, thermometers, SO2 measurement devices, glucose level meters, etc.Often, multiple instruments must be brought to a patient's room by acaretaker and the measurements collected by each instrument. Thismonitoring process can be time consuming, inconvenient and is not alwayscontinuous. It may also disrupt sleep of the patient. The measurementsof the vitals must then be manually recorded into the patient'selectronic medical record.

In addition, detection of substances and measurement of concentrationlevel or indicators of various substances in a patient's blood vesselsis important in health monitoring. Currently, detection of concentrationlevels of blood substances is performed by drawing blood from a bloodvessel using a needle and syringe. The blood sample is then transportedto a lab for analysis. This type of monitoring is invasive,non-continuous and time consuming.

One current non-invasive method is known for measuring the oxygensaturation of blood using pulse oximeters. Pulse oximeters detect oxygensaturation of hemoglobin by using, e.g., spectrophotometry to determinespectral absorbencies and determining concentration levels of oxygenbased on Beer-Lambert law principles. In addition, pulse oximetry mayuse photoplethysmography (PPG) methods for the assessment of oxygensaturation in pulsatile arterial blood flow. The subject's skin at a‘measurement location’ is illuminated with two distinct wavelengths oflight and the relative absorbance at each of the wavelengths isdetermined. For example, a wavelength in the visible red spectrum (forexample, at 660 nm) has an extinction coefficient of hemoglobin thatexceeds the extinction coefficient of oxihemoglobin. At a wavelength inthe near infrared spectrum (for example, at 940 nm), the extinctioncoefficient of oxihemoglobin exceeds the extinction coefficient ofhemoglobin. The pulse oximeter filters the absorbance of the pulsatilefraction of the blood, i.e. that due to arterial blood (AC components),from the constant absorbance by nonpulsatile venous or capillary bloodand other tissue pigments (DC components), to eliminate the effect oftissue absorbance to measure the oxygen saturation of arterial blood.Such PPG techniques are heretofore been limited to determining oxygensaturation.

As such, there is a need for a patient monitoring system that includes acontinuous and non-invasive biosensor that measures patient vitals andmonitors concentration levels or indicators of one or more substances inblood flow.

SUMMARY

According to a first aspect, a biosensor is attached to the health careband. The biosensor includes a memory configured to store a uniquepatient identification, a temperature sensor configured to obtain a skintemperature of the patient, and a PPG circuit. The PPG circuit detects aconcentration level of nitric oxide (NO) in arterial blood flow of thepatient and determines biosensor data of the patient, wherein thebiosensor data includes oxygen saturation levels, hemoglobin levels orheart rate. A wireless transceiver transmits the skin temperature,biosensor data, the NO concentration level and the unique patientidentification to one or more remote devices. The PPG circuit is furtherconfigured to emit light at a plurality of wavelengths directed at skinof the patient and obtain a plurality of spectral responses at each ofthe plurality of wavelengths from light reflected from the skin. Aprocessing circuit determines the biosensor data using at least one ofthe plurality of spectral responses and determines the concentrationlevel of NO in arterial blood flow using at least another one of theplurality of spectral responses.

According to a second aspect, a biosensor configured for attachment to apatient including a memory configured to store a unique patientidentification and a PPG circuit configured for obtaining aconcentration level of nitric oxide (NO) in arterial blood flow of thepatient. The PPG circuit is configured to generate at least a firstspectral response for light reflected around a first wavelength fromskin tissue of the patient, wherein the first wavelength is responsiveto nitric oxide (NO) levels in arterial blood flow and generate at leasta second spectral response for light detected around a second wavelengthreflected from the skin tissue of the patient, wherein the secondwavelength has a low absorption coefficient for nitric oxide (NO) inarterial blood flow. A processing circuit processes the first and secondspectral responses at the first wavelength and the second wavelength andobtains a concentration level of NO in the arterial blood flow of thepatient. A wireless transceiver transmits the concentration level of NOand the unique patient identification to one or more devices.

According to a third aspect, a biosensor is attached to a patient andincludes a memory configured to store a unique patient identificationand a PPG circuit configured to detect a concentration level of nitricoxide (NO) in arterial blood flow of the patient and determine biosensordata of the patient, wherein the biosensor data includes oxygensaturation levels, hemoglobin levels or heart rate. A wirelesstransceiver transmits the biosensor data, the NO concentration level andthe unique patient identification to one or more devices in anelectronic medical record (EMR) network. The biosensor further includesa temperature sensor configured to detect a temperature of the patientand an activity monitoring circuit configured to detect an activitylevel of the patient. The biosensor monitors the biosensor data and theNO concentration level of the patient during an admission period of thehealth care facility and periodically transmits the biosensor data, theNO concentration level and the unique patient identification of thepatient at periodic intervals to the EMR system during the admissionperiod. The biosensor of claim is further configured to analyze thebiosensor data and the NO concentration level during the admissionperiod of the health care facility of the patient to track efficacy ofone or more treatments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A illustrates a perspective view of an embodiment of a known armband for tracking of a patient.

FIG. 1B illustrates a perspective view of a scanner and a scanningprocess of a barcode on the known arm band.

FIG. 1C illustrates a perspective view of an embodiment of a vitalsmonitoring cart.

FIG. 2 illustrates a perspective view of an embodiment of a health careband.

FIG. 3 illustrates a schematic block diagram of an exemplary embodimentof a biosensor.

FIG. 4 illustrates a schematic block diagram illustrating an embodimentof the PPG circuit in more detail.

FIG. 5 illustrates a schematic block diagram of another exemplaryembodiment of the the PPG circuit.

FIG. 6 illustrates a schematic block diagram of an embodiment of the PPGcircuit with a plurality of photodetectors.

FIG. 7 illustrates a schematic diagram of a graph of actual clinicaldata obtained using PPG techniques at a plurality of wavelengths.

FIG. 8 illustrates a logical flow diagram of an embodiment of a methodof the biosensor.

FIG. 9 illustrates a logical flow diagram of an embodiment of a methodof determining concentration levels of one or more substances in moredetail.

FIG. 10 illustrates a schematic block diagram of another embodiment of abiosensor using a broad spectrum light source.

FIG. 11A illustrates a graph of an embodiment of an output of a broadspectrum light source.

FIG. 11B illustrates a graph with an embodiment of an exemplary spectralresponse of detected light across a broad spectrum.

FIG. 12 illustrates a logical flow diagram of an exemplary method todetermine blood concentration levels of a plurality of substances usingthe spectral response for a plurality of wavelengths.

FIG. 13 illustrates a logical flow diagram of an exemplary method todetermine blood concentration levels of a single substance using thespectral response for a plurality of wavelengths.

FIG. 14 illustrates a schematic block diagram of an embodiment of amethod 1400 for determining concentration levels or indicators ofsubstances in pulsating blood flow in more detail.

FIG. 15 illustrates a logical flow diagram of an exemplary method todetermine an absorption coefficients μ of a substance at a wavelength λ.

FIG. 16A and FIG. 16B illustrate perspective views of another embodimentof the health care band.

FIG. 17A illustrates an exemplary embodiment of another form factor ofthe biosensor.

FIG. 17B illustrates an exemplary embodiment of another form factor ofthe biosensor.

FIG. 18 illustrates an exemplary embodiment of another form factor ofthe biosensor.

FIG. 19A illustrates an exemplary embodiment of another form factor ofthe biosensor.

FIG. 19B illustrates an exemplary embodiment of another form factor ofthe biosensor.

FIG. 20 illustrates a schematic block diagram of an embodiment of anexemplary network in which the the biosensor described herein mayoperate.

FIG. 21A illustrates a schematic block diagram of an embodiment of anetwork illustrating interoperability of a plurality of bio sensors.

FIG. 21B illustrates a logical flow diagram of an embodiment of a methodfor adjusting operation of the biosensor in response to a position ofthe biosensor.

FIG. 22 illustrates a schematic drawing of an exemplary embodiment ofresults of clinical data obtained using an embodiment of the biosensorfrom a first patient.

FIG. 23 illustrates a schematic drawing of another exemplary embodimentof results of clinical data obtained using an embodiment of thebiosensor from a second patient.

FIG. 24 illustrates a schematic drawing of another exemplary embodimentof results of clinical data obtained using an embodiment of thebiosensor from a third patient.

FIG. 25 illustrates a schematic drawing of another exemplary embodimentof results of clinical data obtained using the biosensor from a fourthpatient.

FIG. 26 illustrates an exemplary graph of spectral responses of aplurality of wavelengths from clinical data using the biosensor.

FIG. 27 illustrates a logical flow diagram of an embodiment of a methodto determine a presence of an infection by the biosensor.

FIG. 28 illustrates a schematic block diagram of an embodiment of amethod for using the biosensor throughout the health care management ofa patient.

DETAILED DESCRIPTION

The word “exemplary” or “embodiment” is used herein to mean “serving asan example, instance, or illustration.” Any implementation or aspectdescribed herein as “exemplary” or as an “embodiment” is not necessarilyto be construed as preferred or advantageous over other aspects of thedisclosure. Likewise, the term “aspects” does not require that allaspects of the disclosure include the discussed feature, advantage, ormode of operation.

Embodiments will now be described in detail with reference to theaccompanying drawings. In the following description, numerous specificdetails are set forth in order to provide a thorough understanding ofthe aspects described herein. It will be apparent, however, to oneskilled in the art, that these and other aspects may be practicedwithout some or all of these specific details. In addition, well knownsteps in a method of a process may be omitted from flow diagramspresented herein in order not to obscure the aspects of the disclosure.Similarly, well known components in a device may be omitted from figuresand descriptions thereof presented herein in order not to obscure theaspects of the disclosure.

FIG. 1A illustrates a perspective view of an embodiment of a known armband 10 for tracking of a patient. The arm band 10 includes a barcode 12that is printed with a unique patient identification 18. The arm bandmay include other patient information such as a patient name 14 and dateof birth 16. A hospital or other health care facility associates theunique patient identification with a patient and uses the patientidentification to identify an electronic medical record (EMR), alsoknown as an electronic health record (EHR), for the patient and fortracking administration of medicine, vitals, procedures, etc.

FIG. 1B illustrates a perspective view of a scanner 20 and a scanningprocess of the barcode 12 on the arm band 10. To track the patient'sidentification, the barcode 12 must be physically scanned by a scanner20 to confirm the patient identification prior to monitoring orrecording vitals, administration of medicine or treatments, performingprocedures, etc. Thus, a caretaker must have a physical scanner 20 toscan the barcode 12 to identify the patient prior to administering themedicine, recording vitals, performing procedures, etc. This processrequires a separate scanner 20 and is time consuming and cumbersome toperform.

FIG. 1C illustrates a perspective view an embodiment of a vitalsmonitoring cart 22. The vitals cart 22 includes multiple instruments,such as a blood pressure cuff, thermometer, and/or a pulse oximeter. Ingeneral, such a vitals cart 22 must be wheeled into a patient's roomperiodically, e.g. every 1-4 hours. The caretaker must scan the bar code12 on the armband 10 of the patient using the separate scanner 20. Thenthe caretaker must use each separate instrument to determine a patient'svitals, such as blood pressure, temperature, pulse rate and blood oxygenlevel. These measurements must then be manually input into a computer,laptop, etc. to be included in the patient's electronic medical record(EMR). This process is time consuming, disturbs a patient's sleep, isonly performed periodically, requires multiple instruments, and manualintervention.

In addition, a caretaker may need to periodically take blood samples ofthe patient to determine other health measurements, such as glucoselevels, liver enzyme levels, etc. Often, multiple blood samples must betaken from a patient throughout a day. This process is painful for thepatient, time consuming, inconvenient and is not continuous.

As such, there is a need for a patient tracking system that includes acontinuous and non-invasive biosensor that may measure a patient'svitals, such as pulse, blood pressure, temperature, as well asconcentration of certain substances in the blood, such as insulinresistance or glucose levels, liver enzymes, analytes, or othersubstances.Overview

A non-invasive and continuous biosensor is implemented in a compact formfactor, such as on a wrist band. Due to its compact form factor, thebiosensor may be configured for measurements on various skin surfaces ofa patient, including on a forehead, arm, wrist, abdominal area, chest,leg, ear lobe, finger, toe, ear canal, etc. The biosensor includes amemory that stores a patient identification number and patientinformation, such as name and date of birth, as well as an EMR of thepatient. The biosensor includes a near field communication transceiver,such as an RFID transceiver, for wirelessly communicating the patientidentification information. The patient identification may thus beeasily communicated for admissions, tracking of the patient, recordingadministration of medication, tracking medical procedures, trackinginventory, tracking care management of the patient, billing, and otherfunctions.

In addition, the biosensor includes one or more sensors for detectingbiosensor data, such as a patient's vitals, activity levels, orconcentrations of substances in the blood flow of the patient. Forexample, the biosensor may include a temperature sensor having an arrayof sensors positioned adjacent to the skin of the patient. The biosensormay also include an activity monitor to determine activity level and/orpositioning of the patient. The biosensor may also include aphotoplethysmograpy (PPG) sensor. The PPG sensor may be configured todetect oxygen saturation (SPO₂) levels in blood flow, as well as heartrate and blood pressure. In addition, the PPG sensor is configured tomonitor concentration levels or indicators of one or more substances inthe blood flow of the patient, such as insulin resistance, glucoselevels, liver enzymes, analytes, white blood cell count, alcohol levels,or other substances. In another aspect, the PPG sensor may detectcirculation problems and sleep apnea.

The biosensor data obtained by the biosensor may be associated with thepatient identification and wirelessly communicated to one or more otherdevices for monitoring and updating of the patient's EMR.

Embodiment—Arm Band with Biosensor

FIG. 2 illustrates a perspective view of an embodiment of a health careband 50. The health care band 50 is equipped with a biosensor 100 thatincludes one or more sensors for collecting vitals of a patient. Thebiosensor 100 includes a wireless transmitter that is configured tocommunicate with a healthcare facility network or other LAN, MAN or WANas well as a near field communication transceiver, such as an RFIDtransceiver, to communicate with local devices. The biosensor 100 storesa unique identification of the patient that may be programmed atadmission to the hospital or upon assignment of the health care band 500to the patient. The unique identification is associated with thepatient's EMR such that biosensor data obtained by the biosensor 100 maybe transmitted with the patient's unique identification for monitoringor storage in the patient's EMR.

The biosensor 100 is configured to monitor patient vitals, activitylevels and detect indicators or concentration levels of one or moresubstances in the blood of the patient. The patient's vitals are thusmonitored by the biosensor on the armband without manual intervention oradditional instruments or drawing blood of the patient. The biosensormay be used to track progress of the patient throughout treatment at ahospital or other healthcare facility and provide medical alerts tonotify when vitals are critical.

The health care band 50 may be configured with an adjustable band forplacement or attachment to a patient on an arm, on one or more fingers,around a leg, etc. The health care band 50 may be disposable and uniqueto each patient. In addition, the health care band 50 may also include abarcode 12 for compatibility with existing systems or forduplication/back-up purposes.

In one aspect, the biosensor 100 is removeably attached to the healthcare band 50 using an attachment mechanism 52. For example, theattachment mechanism 52 may include clips or a holder that the bandslides through or other means for attachment and detachment of thebiosensor 100 to the health care band 50.

Embodiment—Biosensor Components

FIG. 3 illustrates a schematic block diagram of an exemplary embodimentof a biosensor 100. The biosensor 100 includes one or more processingcircuits 102 communicatively coupled to a memory device 104. In oneaspect, the memory device 104 may include one or more non-transitoryprocessor readable memories that store instructions which when executedby the processing circuit 102, causes the processing circuit 102 toperform one or more functions described herein. The memory device 104may also include an EEPROM to store a patient identification (ID) 172that is associated with a patient being monitored by the biosensor 100.The memory device 104 may also store an electronic medical record (EMR)or portion of the EMR associated with the patient being monitored by thebiosensor 100. The biosensor data obtained by the biosensor 100 may bestored in the EMR as well as the patient medical history. The processingcircuit 102 may be co-located with one or more of the other circuits inthe biosensor 100 in a same physical encasement or located separately ina different physical encasement or located remotely. In an embodiment,the biosensor 100 is battery operated and includes a battery 108, suchas a lithium ion battery. The biosensor 100 may also include a displayconfigured to display the biosensor data.

The biosensor 100 further includes a transceiver 106. The transceiver106 may include a wireless or wired transceiver configured tocommunicate with one or more devices over a LAN, MAN and/or WAN. In oneaspect, the wireless transceiver may include IEEE 802.11ah, Zigbee, IEEE802.15-11 or WLAN (such as an IEEE 802.11 standard protocol) complianttransceiver. In another aspect, the wireless transceiver may alsoinclude or alternatively include an interface for communicating over acellular network. In an embodiment, the wireless transceiver may includea thin foil for an antenna that is specially cut and includes a carbonpad contact to a main PCB of the biosensor 100. This type of antenna isinexpensive to manufacture and may be printed on the inside of anenclosure for the biosensor 100 situated away from the skin of thepatient to minimize absorption. The transceiver 106 may also include awired transceiver interface, e.g., a USB port or other type of wiredconnection, for communication with one or more other devices over a LAN,MAN and/or WAN.

The biosensor 100 includes one or more types of sensors, such as a PPGcircuit 110, a temperature sensor 112 or an activity monitoring circuit114. The temperature sensor 112 is configured to detect a temperature ofa patient. For example, the temperature sensor 112 may include an arrayof sensors (e.g., 16×16 pixels) positioned on a side of the biosensor100 such that the array of sensors are adjacent to the skin of thepatient. The array of sensors then detects an indication of thetemperature of the patient from the skin.

The activity monitoring circuit 114 is configured to monitor theactivity level of the patient. For example, the activity monitoringcircuit 114 may include a multiple axes accelerometer that measures aposition of the patient and motion of the patient. In one aspect, theactivity monitoring circuit 114 determines periods of activity and rest.For example, the activity monitoring circuit 114 monitors and recordsperiods of rest that meet a predetermined threshold of low motion oractivity level, such as sitting, lying, sleeping, etc. The activitymonitoring circuit 114 may also monitor and record periods of activitythat meet a predetermined threshold of motion or activity level, such aswalking, running, lifting, squatting, etc. The biosensor 100 is thenconfigured to measure and store the patient vitals with an indicator ofthe activity level of the patient. For example, blood oxygen levels mayvary greatly in patients with COPD during rest and activity. The vitalsof the patient are tracked during periods of activity and rest and thelevel of activity at time of measuring the vitals is recorded. Thebiosensor 100 is thus configured to associate measurements of patientvitals with the activity level of the patient.

In another aspect, to help lower power consumption, in an embodiment,the biosensor 100 includes a rest mode. For example, the activitymonitoring circuit 114 may signal a rest mode when a patient is asleepor meets a predetermined threshold of low activity level for apredetermined time period. In the rest mode, the biosensor 100 signalsone or more modules to halt non-essential processing functions. When theactivity monitoring circuit 114 detects a higher activity levelexceeding another predetermined threshold for a predetermined timeperiod, the the biosensor 100 signals one or more modules to exit restmode and resume normal functions. This activity monitoring feature helpsto save power and extend battery life of the biosensor 100.

In another aspect, the activity monitoring circuit is configured toinclude a fitness tracker application. The activity monitoring circuit114 may monitor a number of steps of the patient, amount and length ofperiods of sleep, amount and length of periods of rest, amount andlength of periods of activity, etc.

The biosensor 100 may also include an integrated drug delivery system116 or be communicatively coupled to a drug delivery system 116. Thebiosensor 100 may be configured to control delivery of medicine to apatient based on biosensor data obtained by the biosensor 100 asdescribed in more detail in U.S. Provisional Application No. 62/383,313entitled, “System and Method for a Drug Delivery and Biosensor Patch,”filed Sep. 2, 2016, which is expressly incorporated by reference herein.

The biosensor 100 may include a display 118. The biosensor 100 isconfigured to display a graphical user interface (GUI) that includesbiosensor data.

The biosensor 100 also includes a near field transceiver 120 that mayoperate using RFID, short range radio frequency, Bluetooth, infraredlink, or other short range wireless communication protocol. The nearfield transceiver 120 may transmit the patient identification andbiosensor data over a short range to local devices.

The biosensor 100 also includes a PPG circuit 110. The PPG circuit 110may be configured to detect oxygen saturation (SaO₂ or SpO₂) levels inblood flow, as well as heart rate and blood pressure. In addition, thePPG circuit 110 is configured to detect concentration levels orindicators of one or more substances in the blood flow of the patient asdescribed in more detail herein.

Embodiment—PPG Circuit

FIG. 4 illustrates a schematic block diagram illustrating an embodimentof the PPG circuit 110 in more detail. The PPG circuit 110 implementsphotoplethysmography (PPG) techniques for obtaining concentration levelsor indicators of one or more substances in pulsating arterial bloodflow. The PPG circuit 110 includes a light source 120 having a pluralityof light sources, such as LEDs 122 a-n, configured to emit light throughat least one aperture 128 a. The PPG circuit 110 is configured to directthe emitted light at an outer or epidermal layer of skin tissue of apatient. The plurality of light sources are configured to emit light inone or more spectrums, including infrared (IR) light, ultraviolet (UV)light, near IR light or visible light, in response to driver circuit118. For example, the biosensor 100 may include a first LED 122 a thatemits visible light and a second LED 122 b that emits infrared light anda third LED 122 c that emits UV light, etc. In another embodiment, oneor more of the light sources 122 a-n may include tunable LEDs or lasersoperable to emit light over one or more frequencies or ranges offrequencies or spectrums in response to driver circuit 118.

In an embodiment, the driver circuit 118 is configured to control theone or more LEDs 122 a-n to generate light at one or more frequenciesfor predetermined periods of time. The driver circuit 118 may controlthe LEDs 122 a-n to operate concurrently or progressively. The drivercircuit 118 is configured to control a power level, emission period andfrequency of emission of the LEDs 122 a-n. The biosensor 100 is thusconfigured to emit one or more frequencies of light in one or morespectrums that is directed at the surface or epidermal layer of the skintissue of a patient.

The PPG circuit 110 further includes one or more photodetector circuits130 a-n. For example, a first photodetector circuit 130 may beconfigured to detect visible light and the second photodetector circuit130 may be configured to detect IR light. The first photodetectorcircuit 130 and the second photodetector circuit 130 may also include afirst filter 160 and a second filter 162 configured to filter ambientlight and/or scattered light. For example, in some embodiments, onlylight received at an approximately perpendicular angle to the skinsurface of the patient is desired to pass through the filters. The firstphotodetector circuit 130 and the second photodetector circuit 132 arecoupled to a first A/D circuit 138 and a second A/D circuit 140. The A/Dcircuits 138 and 140 may also include an amplifier and other componentsneeded to generate the spectral response. In another aspect, theplurality of photodetectors 130 is coupled in parallel to a singleamplifier and A/D circuit 138. The light detected by each of thephotodetectors 130 is thus added and amplified to generate a singlespectral response.

In another embodiment, a single photodetector circuit 130 may beimplemented operable to detect light over multiple spectrums orfrequency ranges. For example, the photodetector circuit 130 may includea Digital UV Index/IR/Visible Light Sensor such as Part No. Si1145 fromSilicon Labs™.

The one or more photodetector circuits 130 include a spectrometer orother type of circuit configured to detect an intensity of light as afunction of wavelength or frequency to obtain a spectral response. Theone or more photodetector circuits 130 detects the intensity of lighteither transmitted through or reflected from tissue of a patient thatenters one or more apertures 128 b-n of the biosensor 100. For example,the light may be detected from transmissive absorption (e.g., through afingertip or ear lobe) or from reflection (e.g., reflected from aforehead or stomach tissue). The photodetector circuits 130 then obtaina spectral response of the detected light by measuring the intensity oflight either transmitted or reflected to the photodiodes.

FIG. 5 illustrates a schematic block diagram of another exemplaryembodiment of the the PPG circuit 110. In this embodiment, the biosensor100 is configured for emitting and detecting light through one or moreoptical fibers 152 a-c. The PPG circuit 110 is optically coupled to aplurality of optical fibers 152 a-c. In an embodiment, the plurality ofoptical fibers 152 includes a first optical fiber 152 a opticallycoupled to the light source 120. An optical coupler (not shown) tospread the angle of light emitted from the optical fiber 152 a may alsobe implemented. The optical fiber 152 a may have a narrow viewing anglesuch that an insufficient area of skin surface is exposed to the light.An optical coupler 162 may be used to widen the viewing angle toincrease the area of skin surface exposed to the light.

A second optical fiber 152 b is optically coupled to a firstphotodetector circuit 130 and a third optical fiber 152 c is opticallycoupled to the second photodetector circuit 132. Other configurationsand numbers of the plurality of optical fibers 152 may also beimplemented.

In one aspect, the plurality of optical fibers 152 is situated within anouter ear canal to transmit and detect light in the ear canal. A lightcollimator 116, such as a prism, may be used to align a direction of thelight emitted from the light source 120. One or more filters 160 mayoptionally be implemented to receive the reflected light 142 from theplurality of optical fibers 152 b, 152 c. However, the filters 160 maynot be needed as the plurality of optical fibers 152 b, 152 c may besufficient to filter ambient light and/or scattered light.

FIG. 6 illustrates a schematic block diagram of an embodiment of the PPGcircuit 110 with a plurality of photodetectors 130. In one aspect, theplurality of photodetectors 130 are situated in different physicalpositions and orientations in the biosensor 100. For example, at leastfour photodetectors 130 a, 130 b, 130 c and 130 d are situated in thebiosensor 100 in four different physical positions in a North-South andEast-West orientation or polarity. The output signals of the pluralityof photodetectors are coupled in parallel to the amplifier and A/Dcircuit 138. The light signals detected by each of the photodetectors130 through an aperture 128 in the biosensor are added and amplified togenerate a single spectral response. The spectral response is thus morerobust and less affected by motion artifacts and movement of thebiosensor 100 on the health care band 50. The LEDs 122 a-n may besituated centrally to the physical position of the plurality ofphotodetectors. The temperature sensor 112 may also be physicallysituated near the PPG circuit 110 to detect temperature through a sameaperture 128.

Embodiment—PPG Measurement of Arterial Blood Flow

One or more of the embodiments of the biosensor 100 described herein areconfigured to detect a concentration level or indicator of one or moresubstances within blood flow, such as analyte levels, nitric oxidelevels, insulin resistance or insulin response after caloric intake andpredict diabetic risk or diabetic precursors. The biosensor 100 maydetect insulin response, vascular health, cardiovascular sensor,cytochrome P450 proteins (e.g. one or more liver enzymes or reactions),digestion phase 1 and 2 or caloric intake. The biosensor 100 may even beconfigured to detect proteins or other elements or compounds associatedwith cancer. The biosensor 100 may also detect various electrolytes andmany common blood analytic levels, such as bilirubin amount and sodiumand potassium. For example, the biosensor 100 may detect sodium NACLconcentration levels in the arterial blood flow to determinedehydration. The biosensor 100 may also detect blood alcohol levels invivo in the arterial blood flow. Because blood flow to the skin can bemodulated by multiple other physiological systems, the PPG sensor 110may also be used to monitor breathing, hypovolemia, and othercirculatory conditions. The biosensor 100 may also detect bloodpressure, peripheral oxygen (SpO₂ or SaO₂) saturation, heart rate,respiration rate or other patient vitals. The PPG circuit 110 may alsobe used to detect sleep apnea based on oxygen saturation levels andactivity monitoring during sleep.

In use, the biosensor 100 performs PPG techniques using the PPG circuit110 to detect the concentration levels of substances in blood flow. Inone aspect, the biosensor 100 analyzes reflected visible or IR light toobtain a spectrum response such as, the resonance absorption peaks ofthe reflected visible, UV or IR light. The spectrum response includesspectral lines that illustrate an intensity or power or energy at awavelength or range of wavelengths in a spectral region of the detectedlight.

The ratio of the resonance absorption peaks from two differentfrequencies can be calculated and based on the Beer-Lambert law used toobtain various levels of substances in the blood flow. First, thespectral response of a substance or substances in the arterial bloodflow is determined in a controlled environment, so that an absorptioncoefficient α_(g1) can be obtained at a first light wavelength λ₁ and ata second wavelength λ₂. According to the Beer-Lambert law, lightintensity will decrease logarithmically with path length l (such asthrough an artery of length l). Assuming then an initial intensityI_(in) of light is passed through a path length l, a concentration C_(g)of a substance may be determined using the following equations:At the first wavelength λ₁ ,I ₁ =I _(in1*)10^(−(α) ^(g1) ^(C) ^(gw)^(+α) ^(w1) ^(C) ^(w) ^()*l)At the second wavelength λ₂ ,I ₂ =I _(in2*)10^(−(α) ^(g2) ^(C) ^(gw)^(+α) ^(w2) ^(C) ^(w) ^()*l)wherein:

I_(in1) is the intensity of the initial light at λ₁

I_(in2) is the intensity of the initial light at λ₂

α_(g1) is the absorption coefficient of the substance in arterial bloodat λ₁

α_(g2) is the absorption coefficient of the substance in arterial bloodat λ₂

α_(w1) is the absorption coefficient of arterial blood at λ₁

α_(w2) is the absorption coefficient of arterial blood at λ₂

C_(gw) is the concentration of the substance and arterial blood

C_(w) is the concentration of arterial blood

Then letting R equal:

$R = \frac{\log\; 10( \frac{I\; 1}{I\mspace{14mu}{in}\mspace{14mu} 1} )}{\log\; 10( \frac{I\; 2}{I\mspace{14mu}{in}\mspace{14mu} 2} )}$

The concentration of the substance Cg may then be equal to:

${Cg} = {\frac{Cgw}{{Cgw} + {Cw}} = \frac{{\alpha_{w\; 2}R} - \alpha_{w\; 1}}{{( {\alpha_{w\; 2} - \alpha_{{gw}\; 2}} )*R} - ( {\alpha_{w\; 1} - \alpha_{{gw}\; 1}} )}}$

The biosensor 100 may thus determine the concentration of varioussubstances in arterial blood using spectroscopy at two differentwavelengths using Beer-Lambert principles.

The biosensor 100 determines concentration of one or more substancesusing Beer-Lambert principles. The biosensor 100 transmits light atleast at a first predetermined wavelength and at a second predeterminedwavelength. The biosensor 100 detects the light (reflected from the skinor transmitted through the skin) and analyzes the spectral response atthe first and second wavelengths to detect an indicator or concentrationlevel of one or more substances in the arterial blood flow. In general,the first predetermined wavelength is selected that has a highabsorption coefficient for the targeted substance while the secondpredetermined wavelength is selected that has a low absorptioncoefficient for the targeted substance. Thus, it is generally desiredthat the spectral response for the first predetermined wavelength have ahigher intensity level than the spectral response for the secondpredetermined wavelength.

In another aspect, the biosensor 100 may transmit light at the firstpredetermined wavelength and in a range of approximately 1 nm to 50 nmaround the first predetermined wavelength. Similarly, the biosensor 100may transmit light at the second predetermined wavelength and in a rangeof approximately 1 nm to 50 nm around the second predeterminedwavelength. The range of wavelengths is determined based on the spectralresponse since a spectral response may extend over a range offrequencies, not a single frequency (i.e., it has a nonzero linewidth).The light that is reflected or transmitted light by the target substancemay by spread over a range of wavelengths rather than just the singlepredetermined wavelength. In addition, the center of the spectralresponse may be shifted from its nominal central wavelength or thepredetermined wavelength. The range of 1 nm to 50 nm is based on thebandwidth of the spectral response line and should include wavelengthswith increased light intensity detected for the targeted substancearound the predetermined wavelength.

The first spectral response of the light over the first range ofwavelengths including the first predetermined wavelength and the secondspectral response of the light over the second range of wavelengthsincluding the second predetermined wavelengths is then generated. Thebiosensor 100 analyzes the first and second spectral responses to detectan indicator or concentration level of one or more substances in thearterial blood flow at 406.

Photoplethysmography (PPG) is used to measure time-dependent volumetricproperties of blood in blood vessels due to the cardiac cycle. Forexample, the heartbeat affects volume of arterial blood flow and theconcentration of absorption levels being measured in the arterial bloodflow. Over a cardiac cycle, pulsating arterial blood changes the volumeof blood flow in an artery. Incident light I_(O) is directed at a tissuesite and a certain amount of light is reflected or transmitted and acertain amount of light is absorbed. At a peak of arterial blood flow orarterial volume, the reflected/transmitted light I_(L) is at a minimumdue to absorption by the venous blood, nonpulsating arterial blood,pulsating arterial blood, other tissue, etc. At a minimum of arterialblood flow or arterial volume during the cardiac cycle, thetransmitted/reflected light I_(H) is at a maximum due to lack ofabsorption from the pulsating arterial blood.

The biosensor 100 is configured to filter the reflected/transmittedlight I_(L) of the pulsating arterial blood from thetransmitted/reflected light I_(H). This filtering isolates the light dueto reflection/transmission of substances in the pulsating arterial bloodfrom the light due to reflection/transmission from venous (or capillary)blood, other tissues, etc. The biosensor 100 may then measure theconcentration levels of one or more substances from thereflected/transmitted light I_(L) in the pulsating arterial blood.Though the above has been described with respect to arterial blood flow,the same principles described herein may be applied to venous bloodflow.

In general, the relative magnitudes of the AC and DC contributions tothe reflected/transmitted light signal I may be used to substantiallydetermine the differences between the diastolic time and the systolicpoints. In this case, the difference between the reflected light I_(L)and reflected light I_(H) corresponds to the AC contribution of thereflected light (e.g. due to the pulsating arterial blood flow). Adifference function may thus be computed to determine the relativemagnitudes of the AC and DC components of the reflected light I todetermine the magnitude of the reflected light I_(L) due to thepulsating arterial blood. The described techniques herein fordetermining the relative magnitudes of the AC and DC contributions isnot intended as limiting. It will be appreciated that other methods maybe employed to isolate or otherwise determine the relative magnitude ofthe light I_(L) due to pulsating arterial blood flow.

FIG. 7 illustrates a schematic diagram of a graph of actual clinicaldata obtained using PPG techniques at a plurality of wavelengths. Thebiosensor 100 emits light having a plurality of wavelengths during ameasurement period. The light at each wavelength (or range ofwavelengths) may be transmitted concurrently or sequentially. Theintensity of the reflected light at each of the wavelengths (or range ofwavelengths) is detected and the spectral response is measured over themeasurement period. The spectral response 706 for the plurality ofwavelengths obtained using the biosensor in clinical trials is shown inFIG. 7. In this clinical trial, two biosensors 100 attached to twoseparate fingertips of a patient were used to obtain the spectralresponses 706. The first biosensor 100 obtained the spectral responsefor a wavelength at 940 nm 710, a wavelength at 660 nm 712 and awavelength at 390 nm 714. The second biosensor 100 obtained the spectralresponse for a wavelength at 940 nm 716, a wavelength at 592 nm 718 anda wavelength at 468 nm 720.

In one aspect, the spectral response of each wavelength may be alignedbased on the systolic 702 and diastolic 704 points in their spectralresponses. This alignment is useful to associate each spectral responsewith a particular stage or phase of the pulse-induced local pressurewave within the blood vessel (which may mimic the cardiac cycle 706 andthus include systolic and diastolic stages and sub-stages thereof). Thistemporal alignment helps to determine the absorption measurementsacquired near a systolic point in time of the cardiac cycle and near thediastolic point in time of the cardiac cycle 706 associated with thelocal pressure wave within the patient's blood vessels. This measuredlocal pulse timing information may be useful for properly interpretingthe absorption measurements in order to determine the relativecontributions of the AC and DC components measured by the biosensor 110.So for one or more wavelengths, the systolic points 702 and diastolicpoints 704 in the spectral response are determined. These systolicpoints 702 and diastolic points 704 for the one or more wavelengths maythen be aligned as a method to discern concurrent responses across theone or more wavelengths.

In another embodiment, the the systolic points 702 and diastolic points704 in the absorbance measurements are temporally correlated to thepulse-driven pressure wave within the arterial blood vessels—which maydiffer from the cardiac cycle. In another embodiment, the biosensor 100may concurrently measure the intensity reflected at each the pluralityof wavelengths. Since the measurements are concurrent, no alignment ofthe spectral responses of the plurality of wavelengths may be necessary.

FIG. 8 illustrates a logical flow diagram of an embodiment of a method800 of the biosensor 100. In one aspect, the biosensor 100 emits anddetects light at a plurality of predetermined frequencies orwavelengths, such as approximately 940 nm, 660 nm, 390 nm, 592 nm, and468 nm. The light is pulsed for a predetermined period of time (such as100 usec or 200 Hz) sequentially at each predetermined wavelength. Inanother aspect, light may be pulsed in a wavelength range of 1 nm to 50nm around each of the predetermined wavelengths. Then, the spectralresponses are obtained for the plurality of wavelengths at 802. Thespectral response may be measured over a predetermined period (such as300 usec.). This measurement process is repeated sequentially pulsingthe light and obtaining spectral measurements over a desired measurementperiod, e.g. from 1-2 seconds to 1-2 minutes or 2-3 hours orcontinuously over days or weeks. Because the human pulse is typically onthe order of magnitude of one 1 HZ, typically the time differencesbetween the systolic and diastolic points are on the order of magnitudeof milliseconds or tens of milliseconds or hundreds of milliseconds.Thus, spectral response measurements may be obtained at a frequency ofaround 10-100 Hz over the desired measurement period.

A low pass filter (such as a 5 Hz low pass filter) is applied to thespectral response signal at 804. The relative contributions of the ACand DC components are obtained I_(AC+DC) and I_(AC). A peak detectionalgorithm is applied to determine the systolic and diastolic points at706. Beer Lambert equations are applied as described below at 708. Forexample, the L_(λ) values are then calculated for one or more of thewavelengths λ, wherein the L_(λ) values for a wavelength equals:

$L_{\lambda} = {{Log}\; 10( \frac{{IAC} + {DC}}{IDC} )}$wherein I_(AC+DC) is the intensity of the detected light with AC and DCcomponents and I_(DC) is the intensity of the detected light with the ACfiltered by the low pass filter. The value L_(λ) isolates the spectralresponse due to pulsating arterial blood flow, e.g. the AC component ofthe spectral response.

A ratio R of the L_(λ) values at two wavelengths may then be determined.For example,

${{Ratio}\mspace{14mu} R} = \frac{{L\lambda}\; 1}{{L\lambda}\; 2}$

The L_(λ) values and Ratio R may be determined for one or more of thepredetermined measurement periods over a desired time period, e.g. from1-2 seconds to 1-2 minutes or 2-3 hours or continuously over days orweeks to monitor the values. The L_(λ) values and Ratio R may be used todetermine concentration levels of one or more substances in the arterialblood flow as well as patient vitals, such as oxygen saturation SpO2,heart rate, respiration rate, etc.

Embodiment—Determination of Indicators or Concentration Levels of One orMore Substances

In one aspect, based on unexpected results from clinical trials, it wasdetermined that a ratio R_(390,940) obtained at approximately L_(λ1)=390nm and L_(λ2)=940 is useful as a predictor or indicator of diabetic riskor diabetes. For example, during experimental clinical trials, spectralresponses were obtained during predetermined measurement periods over a1-2 minute time period at 390 nm and 940 nm. An R_(390,940) value wasobtained based on the spectral responses measured during a plurality ofthe predetermined measurement periods over the 1-2 minute time period.From the unexpected results of the clinical trials, an average or meanR_(390,940) value of less than 1 (e.g., approximately 0.5) indicatedthat a person has diabetes or early onset of diabetes. An average ormean R_(390,940) value of 2 or above indicated that a person has a lowerrisk of a diabetes diagnosis. An average or mean R_(390,940) value inthe 5-6 range indicated no current risk of diabetes. The R_(390,940)value determined using L_(λ1)=390 nm and L_(λ2)=940 was thus anindicator of diabetic risk and diabetes. Thus, based on the clinicaltrials, a non-invasive, quick 1-2 minute test produced an indicator ofdiabetes or diabetic risk in a person.

In particular, in unexpected results, it is believed that nitric oxideNO levels in the arterial blood flow is being measured at least in partby the biosensor 100 at λ1=390 nm. Since NO is partly in a gaseous formin blood vessels (prior to adhesion to hemoglobin), the total NOconcentration levels of in vitro blood samples, e.g. from a fingerprick, are not detected as the gas dissipates. Thus, the biosensor 100measurements to determine the L_(390 nm) values are the first time NOconcentration levels in arterial blood flow have been measured directlyin vivo. In clinical trials performed as described further herein, inunexpected results, it seems that the NO levels are an indication ofinsulin response in the blood as well as concentration levels of insulinand/or glucose levels in the blood. The L_(λ1=390 nm) and R valueobtained from L_(λ1=390 nm) are thus an indicator of blood glucoselevels, insulin response and diabetic risk as well as vascular health.These unexpected results have advantages in early detection of diabeticrisk and easier, non-invasive monitoring of insulin resistance andglucose levels as well as vascular health and other conditions. Theseresults are discussed in more detail herein with illustrativeexperimental data.

The biosensor 100 may also function as a pulse oximeter using similarprinciples under Beer-lambert law to determine pulse and oxygensaturation levels in pulsating arterial flow. For example, a firstwavelength at approximately 940 nm and a second wavelength atapproximately 660 nm may be used to determine oxygen saturation levels.

The biosensor 100 may also be used to determine alcohol levels in theblood using wavelengths at approximately 390 nm and/or 468 nm. Inanother embodiment, an R_(468,940) value for at leastL_(468 nm)/L_(940 nm) may be used as a liver enzyme indicator, e.g. P450enzyme indicator. In another embodiment, an R_(592,940) value for atleast L_(592 nm)/L_(940 nm) may be used as a digestive indicator tomeasure digestive responses, such as phase 1 and phase 2 digestivestages. The biosensor 100 may also detect other types of electrolytes oranalytes, such as sodium and potassium, using similar PPG techniques. Inanother aspect, the biosensor 100 may detect which blood cell levels inarterial blood flow using similar PPG techniques.

In another aspect, abnormal cells or proteins or compounds that arepresent or have higher concentrations in the blood with persons havingcancer, may be detected using similar PPG techniques described herein atone or more other wavelengths. Thus, cancer risk may then be obtainedthrough non-invasive testing by the biosensor 100.

Since the biosensor 100 may operate in multiple frequencies, varioushealth monitoring tests may be performed concurrently and continuously.These tests may be performed throughout a hospital stay or may benon-invasively and quickly and easily obtained using the biosensor 100in a physician's office or other clinical setting or at home. These andother aspects of the biosensor 100 are described in more detail hereinwith clinical trial results.

FIG. 9 illustrates a logical flow diagram of an embodiment of a method900 of determining concentration levels of one or more substances inmore detail. The biosensor 100 obtains a first spectral response signalincluding a first wavelength and a second response signal including asecond wavelength at 902. In general, the first wavelength is selectedthat has a high absorption coefficient for the targeted substance whilethe second wavelength is selected that has a low absorption coefficientfor the targeted substance. Thus, it is generally desired that thespectral response for the first predetermined wavelength have a higherintensity level than the spectral response for the second predeterminedwavelength.

Each of the spectral response signals includes AC and DC componentsI_(AC+DC). A low pass filter is applied to the spectral response signalsI_(AC+DC) to isolate the DC component of the first and second spectralresponse signals I_(DC). The AC fluctuation is due to the pulsatileexpansion of the arteriolar bed due to the volume increase in arterialblood. In order to measure the AC fluctuation, measurements are taken atdifferent times and a peak detection algorithm or other means is used todetermine the diastolic point and the systolic point of the spectralresponse at 906. The systolic and diastolic measurements are compared inorder to compute the aforementioned R ratio. For example, a logarithmicfunction may be applied to the ratio of I_(AC+DC) and I_(DC) to obtainan L value for the first wavelength L_(λ1) at 908 and for the secondwavelength L_(λ2) at 910. The ratio R of the L_(λ) values may then becalculated at 912.

FIG. 10 illustrates a schematic block diagram of another embodiment of abiosensor 100 using a broad spectrum light source 1020. In one aspect,the biosensor 100 may include a broad spectrum light source 1020, suchas a white light to infrared (IR) or near IR LED 1022, that emits lightwith wavelengths from e.g. 350 nm to 2500 nm. Broad spectrum lightsources with different ranges may be implemented. In an aspect, a broadspectrum light source with a range across 100 nm wavelengths to 2000 nmrange of wavelengths in the visible, IR and/or UV frequencies. Forexample, a broadband tungsten light source for spectroscopy may be used.The spectral response of the reflected light is then measured across thewavelengths in the broad spectrum, e.g. from 350 nm to 2500 nm,concurrently. In an aspect, a charge coupled device (CCD) spectrometer1030 may be configured to measure the spectral response of the detectedlight over the broad spectrum.

The spectral response of the reflected light is analyzed for a pluralityof wavelengths, e.g. at 10 nm to 15 nm to 20 nm, incremental wavelengthsacross the wavelengths from 10 nm to 2500 nm. For example, theprocessing described with respect to FIG. 9 is performed at theplurality of wavelengths. In one aspect, the L values are calculated atincremental wavelengths, such as at 1 nm or 1.5 nm or 2 nm incrementalwavelengths. This process may be used to determine one or morewavelengths or ranges of wavelengths useful in detection for one or moresubstances in the arterial blood flow. For example, a spectral responsearound a wavelength of 500 nm may have a higher intensity. Trials maythen be conducted to determine the one or more substances in the bloodthat generates this spectral response. In another embodiment, a knownsubstance may be present in the blood and the spectral response acrossthe broad spectrum is then analyzed to determine a pattern orcorrelation of intensities of wavelengths in the spectral response tothe known substance. For example, a pattern of intensities ofwavelengths across a range of wavelengths may indicate the presence of asubstance. The intensities of the wavelengths may then be analyzed todetermine concentration levels of the substance as described in moredetail herein.

In another embodiment, the spectral response is analyzed at a set ofpredetermined wavelengths (or a range of 1 nm to 50 nm including eachpredetermined wavelength). The L values are calculated for the set ofpredetermined wavelengths using the analyzed spectral responses. Theconcentration levels of one or more substances may then be determinedbased on absorption coefficients for the one or more substances at eachof the predetermined wavelengths. The concentration levels of aplurality of substances may be determined using the spectral response ofa plurality of frequencies. The biosensor 100 may thus be used to detecta plurality of substances based on data obtained during a singlemeasurement period. The biosensor 100 may thus perform a blood panelanalysis based on in vivo arterial blood flow in a relatively shortmeasurement period of 1-5 minutes. The blood panel analysis may beperformed in a physician's office to determine results of the test whilethe patient is in the office. The biosensor 100 may thus provide bloodpanel analysis results in a 1-5 minute measurement period without a needfor blood samples and lab tests that may take hours or days or weeks toobtain.

FIG. 11A illustrates a graph of an embodiment of an output of a broadspectrum light source. The relative light intensity or power output ofthe broad spectrum light source is shown versus wavelength of the outputlight I_(O). The light intensity or power of the output light extendsfrom wavelengths of approximately 350 nm to approximately 2500 nm. Thebroad spectrum light source 1020 emits light with power across thewavelengths from 350 nm to 2500 nm. Broad spectrum light sources withdifferent ranges may be implemented. In an aspect, a broad spectrumlight source with a range across 100 nm wavelengths to 2000 nm range ofwavelengths in the visible, IR and/or UV frequencies.

FIG. 11B illustrates a graph with an embodiment of an exemplary spectralresponse of detected light 1104 across a broad spectrum, e.g. fromapproximately 10 nm to 2000 nm. In one aspect, the spectral response ofthe detected light 1104 may be analyzed at a plurality of wavelengths,e.g. at a set of predetermined wavelengths or at incrementalwavelengths. In another aspect, the spectral response of wavelengthswith a detected intensity or power exceeding a predetermined thresholdmay be analyzed. For example, in the graph shown in FIG. 11B, thespectral response at wavelengths of 200 nm, 680 nm and 990 nm (andranges of +/−20 to 50 nm around these wavelengths) exceeding a relativeintensity threshold of 20000 may be analyzed.

Embodiment—Determination of Concentration Levels at a Plurality ofWavelengths

FIG. 12 illustrates a logical flow diagram of an exemplary method 1200to determine blood concentration levels of a plurality of substancesusing the spectral response for a plurality of wavelengths. Thebiosensor 100 transmits light directed at living tissue. The light maybe across a broad spectrum or at a plurality of discrete frequencies orat a single frequency. For example, the light may be emitted using abroad spectrum light source or multiple LEDs transmitting at discretewavelengths or a tunable laser transmitting at one or more frequencies.The spectral response of light (e.g. either transmitted through theliving tissue or reflected by the living tissue) is detected at 1204.The spectral response is analyzed at a plurality of wavelengths (andranges of +/−20 to 50 nm around these wavelengths) at 1206. In oneaspect, the systolic and diastolic points are determined at theplurality of wavelengths and the L values are calculated using thesystolic and diastolic points. In one aspect, the L values aredetermined at incremental wavelengths, such as at 1 nm or 1.5 nm or 2 nmincremental wavelengths. In another aspect, the L values are calculatedfor a set of predetermined wavelengths. A ratio R value may also bedetermined using L values derived from a first spectral responseobtained for a first wavelength (and in one aspect including a range of+/−20 to 50 nm) and a spectral response obtained for a second wavelength(and in one aspect including a ranges of +/−20 to 50 nm).

Using the absorption coefficients associated with the plurality ofsubstances, the concentration levels of a plurality of substances maythen be determined. For example, the intensity of light may be due toabsorption by a plurality of substances in the arterial blood flow. Forexample,LN(I _(1-n))=μ₁ *C ₁+μ₂ *C ₂+μ₃ *C ₃ . . . +μ_(n) *C _(n)wherein,

I_(1-n)=intensity of light at wavelengths κ_(1-n)

μ_(n)=absorption coefficient of substance 1, 2, . . . n at wavelengthsλ_(1-n)

C_(n)=Concentration level of substance 1, 2, . . . n

When the absorption coefficients μ_(1-n) are known at the wavelengthsλ_(1-n), then the concentration levels C_(1-n) of multiple substancesmay be determined.

FIG. 13 illustrates a logical flow diagram of an exemplary method 1300to determine blood concentration levels of a single substance using thespectral response for a plurality of wavelengths. The intensity of lightat a plurality of wavelengths may be due to absorption by a singlesubstance in the arterial blood flow. For example, a single substancemay absorb or reflect a plurality of different wavelengths of light. Inthis example then,LN(I _(1-n))=μ₁ *C+μ ₂ *C+μ ₃ *C . . . +μ _(n) *Cwherein,

I_(1-n)=intensity of light at wavelengths λ_(1-n)

μ_(n)=absorption coefficient of a substance at wavelengths λ_(1-n)

C=Concentration level of a substance

When the absorption coefficients μ_(1-n) of the single substance areknown at the wavelengths λ_(1-n), then the concentration level C of thesubstance may be determined from the spectral response for each of thewavelengths (and in one aspect including a range of 1 nm to 50 nm aroundeach of the wavelengths). Using the spectral response at multiplefrequencies provides a more robust determination of the concentrationlevel of the substance.

In use, the biosensor 100 transmits light directed at living tissue at aplurality of discrete wavelengths or over a broad spectrum at 1302. Thespectral response of light from the living tissue is detected at 1304,and the spectral response is analyzed for a plurality of wavelengths(and in one aspect including a range of +/−20 to 50 nm around each ofthe wavelengths) at 1306. Then, the concentration level C of thesubstance may be determined from the spectral response for each of theplurality of wavelengths at 1308. An example for calculating theconcentration of one or more substances over multiple wavelengths may beperformed using a linear function, such as is illustrated herein below.LN(I _(1-n))=Σ_(i=0) ^(n) μi*Ciwherein,

I_(1-n)=intensity of light at wavelengths λ_(1-n)

μ_(n)=absorption coefficient of substance 1, 2, . . . n at wavelengthsλ_(1-n)

C_(n)=Concentration level of substance 1, 2, . . . n

FIG. 14 illustrates a schematic block diagram of an embodiment of amethod 1400 for determining concentration levels or indicators ofsubstances in pulsating blood flow in more detail. The biosensor 100obtains a spectral response signal at a first wavelength and at a secondwavelength at 1402. The spectral response signal includes AC and DCcomponents IAC+DC. A low pass filter is applied to the spectral responsesignal IAC+DC to isolate the DC component 1406 of the spectral responsesignal at each wavelength at 1404. The AC fluctuation is due to thepulsatile expansion of the arteriolar bed due to the volume increase inarterial blood. In order to measure the AC fluctuation, measurements aretaken at different times and a peak detection algorithm or other meansis used to determine the diastolic point and the systolic point of thespectral response at 1408. The systolic and diastolic measurements arecompared in order to compute the L values using Beer-Lambert equationsat 1410. For example, a logarithmic function may be applied to the ratioof IAC+DC and IDC to obtain an L value for the first wavelength Lλ1 andfor the second wavelength Lλ2. The ratio R of the first wavelength Lλ1and for the second wavelength Lλ2 may then be calculated at 1412. Whenmultiple frequencies are used to determine a concentration level of oneor more substances, the the linear function described herein are appliedat 1416, and the one or more concentration levels of the substances oranalytes are determined at 1418.

In an embodiment, a substances or analyte may be attached in the bloodstream to one or more hemoglobin compounds. The concentration level ofthe hemoglobin compounds may then need to be subtracted from theconcentration level of the substance to isolate the concentration levelof the substance from the hemoglobin compounds. For example, nitricoxide (NO) is found in the blood stream in a gaseous form and alsoattached to hemoglobin compounds. Thus, the measurements at L_(390 nm)to detect nitric oxide may include a concentration level of thehemoglobin compounds as well as nitric oxide.

The hemoglobin compound concentration levels may be determined andsubtracted to isolate the concentration level of the substance at 1420.The hemoglobin compounds include, e.g., Oxyhemoglobin [HbO2],Carboxyhemoglobin [HbCO], Methemoglobin [HbMet], and reduced hemoglobinfractions [RHb]. The biosensor 100 may control the PPG circuit 110 todetect the total concentration of the hemoglobin compounds using acenter frequency of 660 nm and a range of 1 nm to 50 nm. A method fordetermining the relative concentration or composition of different kindsof hemoglobin contained in blood is described in more detail in U.S.Pat. No. 6,104,938 issued on Aug. 15, 2000, which is hereby incorporatedby reference herein.

Various unexpected results were determined from clinical trials usingthe biosensor 100. In one aspect, based on the clinical trials, an Rvalue obtained from the ratio L_(λ1=390 nm/)and L_(λ2=940) was found tobe a predictor or indicator of diabetic risk or diabetes as described inmore detail herein. In another aspect, based on the clinical trials, theR value obtained from the ratio of L_(468 nm)/L_(940 nm), was identifiedas an indicator of the liver enzyme marker, e.g. P450. In anotheraspect, based on the clinical trials, the R value obtained from theratio of L_(592 nm)/L_(940 nm), was identified as an indicator ofdigestion phases, such as phase 1 and phase 2, in the arterial bloodflow. In another aspect, the R value from the ratio ofL_(660 nm)/L_(940 nm), was found to be an indicator of oxygen saturationlevels SpO₂ in the arterial blood flow. In another aspect, it wasdetermined that the biosensor 100 may determine alcohol levels in theblood using spectral responses for wavelengths at 390 and/or 468 nm. Ingeneral, the second wavelength of 940 nm is selected because it has alow absorption coefficient for the targeted substances described herein.Thus, another wavelength other than 940 nm with a low absorptioncoefficient for the targeted substances (e.g. at least less than 25% ofthe absorption coefficient of the targeted substance for the firstwavelength) may be used instead. For example, the second wavelength of940 nm may be replaced with 860 nm that has a low absorption coefficientfor the targeted substances. In another aspect, the second wavelength of940 nm may be replaced with other wavelengths, e.g. in the IR range,that have a low absorption coefficient for the targeted substances. Ingeneral, it is desired that the spectral response for the firstpredetermined wavelength have a higher intensity level than the spectralresponse for the second predetermined wavelength.

In another aspect, it was determined that other proteins or compounds,such as those present or with higher concentrations in the blood withpersons having cancer, may be detected using similar PPG techniquesdescribed herein with biosensor 100 at one or more other wavelengths.Cancer risk may then be determined using non-invasive testing over ashort measurement period of 1-10 minutes. Since the biosensor mayoperate in multiple frequencies, various health monitoring tests may beperformed concurrently. For example, the biosensor 100 may measure fordiabetic risk, liver enzymes, alcohol levels, cancer risk or presence ofother analytes within a same measurement period using PPG techniques.

FIG. 15 illustrates a logical flow diagram of an exemplary method 1500to determine an absorption coefficients μ of a substance at a wavelengthλ. The concentration level of a substance in arterial blood is obtainedusing a known method at 1502. For example, blood may be extracted atpredetermined intervals during a time period and a blood gas analyzermay be used to measure a concentration level of a substance. Thebiosensor 100 emits light at a wavelength (and in one aspect for a rangeof 1 nm-50 nm around the wavelength) and detects a spectral response forthe wavelength (and in one aspect for a range of 1 nm-50 nm around thewavelength). The spectral response for the predetermined wavelength isanalyzed at 1506. The intensity of the detected light is determined. Theintensity of the detected light is compared to the known concentrationlevel of the substance at 1508. The absorption coefficient for thesubstance may then be determined using the Beer-Lambert equationsdescribed herein at 1510.

The above process may be repeated at one or more other frequencies at1512. For example, as described herein, the spectral analysis over arange or at multiple frequencies may be analyzed to determine one ormore frequencies with a higher intensity or power level in response to aconcentration level or presence of the substance. Thus, one or morefrequencies may be analyzed and identified for detection of thesubstance, and the absorption coefficient for the substance determinedat the one or more frequencies.

In another embodiment, the concentration level of a substance may beobtained from predetermined values obtained through experimentation. Forexample, in a calibration phase, a correlation table may be compiledthrough experimentation that includes light intensity values I_(1-n) atone or more wavelengths λ_(1-n) and a corresponding known concentrationlevel for the substance for the light intensity values. In use, thebiosensor 100 detects a spectral response and determines the lightintensity values I_(1-n) at one or more wavelengths λ_(1-n). Thebiosensor 100 then looks up the detected light intensity values I_(1-n)in the correlation table to determine the concentration level of thesubstance.

Embodiment—Biosensor Form Factors

FIG. 16A and FIG. 16B illustrate perspective views of another embodimentof the health care band 50. The health care band 50 may be adjustable tovarying circumferences. The biosensor 100 may be detachable from thehealth care band 50. In one aspect, the biosensor 100 is removeablyattached to the health care band 50 using an attachment mechanism 52.For example, the attachment mechanism 52 may include clips or a holderthat the band slides through or other means for attachment anddetachment of the biosensor 100 to the health care band 50.

For example, during MRI tests, the biosensor 100 may need to be detachedfrom the health care band 50 to minimize metallic substances in the MRIdevice. The biosensor 100 may then be reattached to the health care bandusing the attachment mechanism 52 after the MRI test. In anotherexample, the health care band 50 may need to be replaced if damaged ortorn. The biosensor 100 may be detached from the damaged band andreattached to a new band. The health care band may be disposable andunique to each patient. The health care band 50 may be configured withan adjustable band for placement or attachment to the patient on an arm,on one or more fingers, around a leg, etc. In general, the arm bandshould be secured such that the aperture of the PPG circuit 110 of thebiosensor 100 is positioned against or adjacent to or facing the skin ofthe patient.

Upon admission, a biosensor 100 is programmed with a patientidentification that is associated with a patient's EMR. The biosensor isattached to the patient using the health care band 50. The biosensor 100may then immediately begin to measure a patient's vitals, such as heartrate, pulse, blood oxygen levels, blood glucose or insulin levels, etc.The patient's vitals are then monitored continuously by the biosensor100 on the armband without further manual intervention or additionalinstruments. The biosensor may be used to track progress throughout thepatient care chain and provide medical alerts to notify when vitals arecritical or reach a certain predetermined threshold. The biosensor 100transmits the data measurements to the EMR network for inclusion in thepatient's EMR as well as to a monitoring station, another hospital orphysician's office, etc.

FIG. 17A illustrates an exemplary embodiment of another form factor ofthe biosensor 100. In an embodiment, the biosensor 100 is implemented ona wearable patch 1700. The wearable patch 1700 may include an adhesivebacking to attach to a skin surface of a patient, such as on a hand,arm, wrist, forehead, chest, abdominal area, or other area of the skinor body or living tissue. Alternatively, the wearable patch 1700 may beattached to the skin surface using adhesive tape. A flexible cable 1702may be used to attach an optical head 1704 of the wearable patch 1700 tothe other components of the biosensor 100, such as the wirelesstransceiver 106 and battery 108. Thus, during a magnetic resonanceimaging (MRI) test when metal needs to be minimal, the battery 108 andtransceiver 106 may be temporarily removed. In addition, the flexiblecable 1702 may be used to open the biosensor 100 to replace the battery108.

FIG. 17B illustrates an exemplary embodiment of another form factor ofthe biosensor 100. In this embodiment, the biosensor 100 may be coupledto an attachable bandaid 1710. The attachable bandaid 1710 may beattached via adhesive or adhesive tape to a skin surface of the patient,e.g. finger, forehead, arm, stomach, leg, wrist, etc.

FIG. 18 illustrates an exemplary embodiment of another form factor ofthe biosensor 100. In this embodiment, the biosensor 100 is configuredin an earpiece 1800. The earpiece 1800 includes an earbud 1802. Thebiosensor 100 is configured to transmit light into the ear canal fromone or more optical fibers 152 in the ear bud 1802 and detect light fromthe ear canal using the one or more optical fibers 152.

FIG. 19A illustrates an exemplary embodiment of another form factor ofthe biosensor 100. In this embodiment, the biosensor 100 is configuredto attach to a finger or fingertip using finger attachment 1902. Thefinger attachment 1902 is configured to securely hold a finger that isinserted into the finger attachment 1902. A display 1900 is implementedon the biosensor 100 with a graphical user interface (GUI) that displaysbiosensor data. For example, in use, the biosensor 100 measures bloodglucose levels using the PPG circuit 110. The blood glucose levels arethen displayed using the GUI on the display 1900. The PPG circuit mayalso measure other patient vitals that are displayed on the display1900, such as oxygen saturation levels, temperature, respiration rates,heart rate, blood alcohol levels, digestive response, caloric intake,white blood cell count, electrolyte or other blood analyteconcentrations, liver enzymes, etc. The biosensor 100 may thus providebiosensor data continuously and non-invasively.

FIG. 19B illustrates an exemplary embodiment of another form factor ofthe biosensor 100. In this embodiment, the biosensor 100 is configuredto attach to a finger or fingertip using finger attachment 1906. Thefinger attachment 1906 includes the PPG circuit 110 and is configured tosecurely hold a finger that is inserted into the finger attachment 1906.The finger attachment 1906 may be implemented within the same encasementas the other components of the biosensor 100 or be communicativelycoupled either through a wired or wireless interface to the othercomponents of the biosensor 100. A display 1908 is implemented for thebiosensor 100 with a graphical user interface (GUI) that displaysbiosensor data including blood glucose levels.

The biosensor 100 may be configured to be attached to an ear lobe orother body parts in other form factors. In addition, one or morebiosensors 100 in one or more form factors may be used in combination todetermine biosensor data at one or more areas of the body.

In these or other form factors, the biosensor 100 may store the uniquepatient identification 172 that is generally included as a barcode oncurrent armbands. The biosensor 100 may also store biosensor datameasured by the biosensor 100 or EMR 170 of the patient that may be usedin one or more applications or systems in the health care chain of apatient. For example, the biosensor 100 is programmed with a uniquepatient identification 172 that is assigned to a patient duringadmission to a hospital and is used for tracking of the patient throughthe transceiver 106 of the biosensor 100. As such, a separate scanner isnot needed to track a patient or scan an arm band. The biosensor 100monitors the patient's vitals as part of the care management of thepatient. The patients vitals are used in data analytics for diagnosis,treatment options, monitoring, etc. The patient vitals may be includedin the patient EMR 170 and otherwise used for patient health. Thebiosensor 100 may also communicate with inventory management. Forexample, when a medicine is provided to a patient, this information ofthe medicine and dosage may be provided to the inventory managementsystem. The inventory management system is then able to adjust theinventory of the medicine. The biosensor 100 may thus have these and/oradditional applications.

Embodiment—EMR Network

FIG. 20 illustrates a schematic block diagram of an embodiment of anexemplary network 2000 in which the the biosensor 100 described hereinmay operate. The exemplary network 2000 may include a combination of oneor more networks that are communicatively coupled, e.g., such as a widearea network (WAN) 2002, a wired local area network (LAN) 2004, awireless local area network (WLAN) 2006, or a wireless wide area network(WAN) 2008. The wireless WAN 1228 may include, for example, a 3G or 4Gcellular network, a GSM network, a WIMAX network, an EDGE network, aGERAN network, etc. or a satellite network or a combination thereof. TheWAN 1222 includes the Internet, service provider network, other type ofWAN, or a combination of one or more thereof. The LAN 2004 and the WLANs20066 may operate inside a home 2016 or enterprise environment, such asa physician's office 2018, pharmacy 2020 or hospital 2022 or othercaregiver.

The biosensor 100 may communicate to one or more user devices 2010, suchas a smart phone, laptop, desktop, smart tablet, smart watch, or anyother electronic device that includes a display for illustrating thepatient's vitals. In one aspect, the user device 2010 or biosensor 100may communicate the patient's vitals to a local or remote monitoringstation 2012 of a caregiver or physician.

One or more biosensor 100 s are communicatively coupled to an EMRapplication server 2030 through one or more of user devices and/or theexemplary networks in the EMR network 2000. The EMR server 2030 includesa network interface card (NIC) 2032, a server processing circuit 2034, aserver memory device 2036 and EMR server application 2038. The networkinterface circuit (NIC) 1202 includes an interface for wireless and/orwired network communications with one or more of the exemplary networksin the EMR network 1220. The network interface circuit 1202 may alsoinclude authentication capability that provides authentication prior toallowing access to some or all of the resources of the EMR applicationserver 1200. The network interface circuit 1202 may also includefirewall, gateway and proxy server functions.

One or more of the biosensors 100 are communicatively coupled to an EMRapplication server 1200 through one or more of the exemplary networks inthe EMR network 1220. The EMR application server 1200 includes a networkinterface circuit 1202 and a server processing circuit 1204. The networkinterface circuit (NIC) 1202 includes an interface for wireless and/orwired network communications with one or more of the exemplary networksin the EMR network 1220. The network interface circuit 1202 may alsoinclude authentication capability that provides authentication prior toallowing access to some or all of the resources of the EMR applicationserver 1200. The network interface circuit 1202 may also includefirewall, gateway and proxy server functions.

The EMR application server 1200 also includes a server processingcircuit 2034 and a memory device 2036. For example, the memory device2036 is a non-transitory, processor readable medium that storesinstructions which when executed by the server processing circuit 2034,causes the server processing circuit 2034 to perform one or morefunctions described herein. In an embodiment, the memory device 2036stores a patient EMR 170 that includes biosensor data and historicaldata of a patient associated with the patient ID 172.

The EMR application server 1200 includes an EMR server application 2038.The EMR server application 2038 is operable to communicate with thebiosensors 100 and/or user devices 2010 and monitoring stations 2012.The EMR server application 2038 may be a web-based application supportedby the EMR application server 2030. For example, the EMR applicationserver 2030 may be a web server and support the EMR server application2038 via a website. In another embodiment, the EMR server application2038 is a stand-alone application that is downloaded to the user devices2010 by the EMR application server 2030 and is operable on the userdevices 2010 without access to the EMR application server 2030 or onlyneeds to accesses the EMR application server 2030 for additionalinformation and updates.

In use, the biosensors 100 may communicate patient's biosensor data tothe EMR application server 2030. A biosensor 100 may be programmed witha patient identification 172 that is associated with a patient's EMR170. The biosensor 100 measures the patient's vitals, such as heartrate, pulse, blood oxygen levels, blood glucose levels, etc. and mayalso control an integrated or separate drug delivery system toadminister medications to the patient. The biosensor 100 is configuredto transmit the patient vitals to the EMR application server 2030. TheEMR server application 2038 updates an EMR 170 associated with thepatient identification 172 with the patient vitals.

The EMR application server 2030 may also be operable to communicate witha physician's office 2018 or pharmacy 2016 or other third party healthcare provider over the EMR network 2000 to provide biosensor data andreceive instructions on dosages of medication. For example, the EMRserver application 2038 may transmit glucose level information, heartrate information or pulse rate information or medication dosages orblood concentration levels of one or more relevant substances to aphysician's office 2018. The EMR server application 2038 may also beconfigured to provide medical alerts to notify a user, physician orother caregiver when vitals are critical or reach a certainpredetermined threshold.

The EMR server application 1408 may also receive instructions from adoctor's office, pharmacy 2016 or hospital 2022 or other caregiverregarding a prescription or administration of a dosage of medication.The EMR server application 2038 may then transmit the instructions tothe biosensor 100. The instructions may include a dosage amount, rate ofadministration or frequency of dosages of a medication. The biosensor100 may then control a drug delivery system to administer the medicationautomatically as per the transmitted instructions.

Embodiment—Interoperability of Biosensors and Other Devices

FIG. 21A illustrates a schematic block diagram of an embodiment of anetwork illustrating interoperability of a plurality of biosensors 100.A plurality of biosensors 100 may interface with a patient andcommunicate with one or more of the other biosensor 100 s. Thebiosensors 100 may communicate directly or communicate indirectlythrough a WLAN or other type of network as illustrated in the Network2000 of FIG. 20. For example, a first biosensor 100 a may include a PPGcircuit 110 configured to detect a blood glucose level. For betterdetection, the biosensor 100 a is positioned on a wrist. A secondbiosensor 100 b may include a drug delivery system 116 configured toadminister insulin to the patient 2100 and is positioned on an abdominalarea of the patient 2100. In use, the first biosensor 100 a continuouslymonitors blood glucose levels and then communicates either directly orindirectly the detected levels to the second biosensor 100 b. The secondbiosensor 100 b then administers a dosage of insulin at anadministration rate and/or frequency rate in response to the detectedblood glucose levels.

In another example, one or more biosensor 100 s may communicate directlyor indirectly with one or more other types of medical devices 2102interfacing with a same patient, such as a first medical device 2100 aand a second medical device 2100 b. The first medical device 2102 a mayinclude an insulin pump, e.g. on body insulin pump or catheter tethereddrip system. In use, the biosensor 100 a monitors glucose and/or insulinindicators or concentration levels in the patient using the PPG circuit110. In response to the detected glucose and/or insulinconcentration/indicators, the biosensor 100 a communicates eitherdirectly or indirectly administration instructions to the first medicaldevice 2102 a. The administration instructions may include dosageamount, administration rate and/or frequency rate. In response to theadministration instructions, the first medical device 2102 a administersan insulin infusion to the patient. The first biosensor 100 a maycontinuously monitor glucose/insulin indicators or concentration levelsand provide automatic instructions to the the first medical device 2102a for the administration of insulin.

In another example, a plurality of biosensors 100, such as the firstbiosensor 100 a and the second biosensor 100 b, may be positioned on apatient to monitor an ECG of the patient. The biosensors 100 maycommunicate the ECG measurements directly or indirectly to each other togenerate an electrocardiogram. The electrocardiogram is transmitted toan EMR application server 2030 or monitoring station 2012 or to a userdevice 2010. Based on the electrocardiogram, a doctor or user mayprovide instructions to the second medical device 2102 b. For example,the second medical device 2102 b may include a Pacemaker or drugdelivery system.

In another example, the biosensor 100 a may include a PPG circuit 110configured to detect alcohol levels in arterial blood flow. The userdevice 2010 may include a locking system installed in an ignition systemof a vehicle. In order to start the vehicle, the the biosensor 100 adetects the blood alcohol concentration (BAC) of the patient. Then thebiosensor 100 a determines whether the blood alcohol concentration (BAC)is above or below a preset legal limit. If it is below this limit, thebiosensor 100 a communicates an instruction to the user device 2010 tounlock the ignition to allow starting of the vehicle. If it is above thelimit, the biosensor 100 a instructs the user device 2010 to lock theignition to prevent starting of the vehicle. Since the biosensor 100 ais directly testing the blood alcohol levels, the biosensor 100 a may bemore accurate and convenient than current breathe analyzers.

Embodiment—Adjustments in Response to Positioning of the Biosensor

FIG. 21B illustrates a logical flow diagram of an embodiment of a method2110 for adjusting operation of the biosensor 100 in response to aposition of the biosensor 100. The biosensor 100 may be positioned ondifferent parts of a patient that exhibit different characteristics. Forexample, the biosensor 100 may be positioned on or attached to variousareas of the body, e.g. a hand, a wrist, an arm, forehead, chest,abdominal area, ear lobe, fingertip or other area of the skin or body orliving tissue. The characteristics of underlying tissue vary dependingon the area of the body, e.g. the underlying tissue of an abdominal areahas different characteristics than the underlying tissue at a wrist. Theoperation of the biosensor 100 may need to be adjusted in response toits positioning due to such varying characteristics of underlyingtissue.

The biosensor 100 is configured to obtain position information on apatient at 2112. The position information may be input from a userinterface. In another aspect, the biosensor 100 may determine itspositioning, e.g. using the activity monitoring circuit 114 and/or PPGcircuit 110. For example, the PPG circuit 110 may be configured todetect characteristics of underlying tissue. The biosensor 100 thencorrelates the detected characteristics of the underlying tissue withknown or predetermined characteristics of underlying tissue (e.g.measured from an abdominal area, wrist, forearm, leg, etc.) to determineits positioning. Information of amount and types of movement from theactivity monitoring circuit 114 may be used as well in the determinationof position.

In response to the determined position and/or detected characteristicsof the underlying tissue, the operation of the biosensor 100 is adjustedat 2114. For example, the biosensor 100 may adjust operation of the PPGcircuit 110. The article, “Optical Properties of Biological Tissues: AReview,” by Steven L. Jacques, Phys. Med. Biol. 58 (2013), which ishereby incorporated by reference herein, describes wavelength-dependentbehavior of scattering and absorption of different tissues. The PPGcircuit 110 may adjust a frequency or wavelength in detection of aconcentration level of a substance based on the underlying tissue. ThePPG circuit 110 may adjust an absorption coefficient when determining aconcentration level of a substance based on Beer-Lambert principles dueto the characteristics of the underlying tissue. Other adjustments mayalso be implemented depending on predetermined or measuredcharacteristics of the underlying tissue.

Adjustments to the activity monitoring circuit 114 may need to be madedepending on positioning as well. For example, the type and level ofmovement detected when positioned on a wrist of a patient may vary fromthe type and level of movement when positioned on an abdominal area ofthe patient. In another aspect, the biosensor 100 may adjustmeasurements from the temperature sensor 112 depending on placement ofthe patient, e.g. the sensor array measurements may vary from a wrist orforehead.

The biosensor 100 is thus configured to obtain position information andperform adjustments to its operation in response to the positioninformation.

Embodiment—Diabetic Parameter Measurements

Clinical data obtained using the biosensor 100 is now described herein.The biosensor 100 was used to monitor concentration levels or indicatorsof one or more substances in the blood flow of the patient in theclinical trials over a measurement time period. For example, thebiosensor 100 was used in the clinical trials to non-invasively detectdiabetic parameters, such as insulin response over time, nitric oxide(NO) levels, glucose levels, and predict diabetic risk or diabeticprecursors, in pulsatile arterial blood flow. The biosensor 100 was alsoused to detect blood alcohol levels in pulsatile arterial blood flow.The biosensor 100 was also used to detect digestive parameters, such asdigestion phase 1 and 2 responses. The biosensor 100 also detected heartrate and blood oxygen saturation levels in the clinical trials.

FIG. 22 illustrates a schematic drawing of an exemplary embodiment ofresults of clinical data 2200 obtained using an embodiment of thebiosensor 100 from a first patient. This first patient is a 42 year oldfemale with no known diagnosis of diabetes or other conditions. Abiosensor 100 is placed on at least one finger of the first patient andthe spectral response is measured over the least three wavelengths at390 nm, 660 nm and 940 nm (and also in range of 1 nm to 50 nm). Thegraph 2006 illustrates the spectral response or frequency spectrum dataobtained for the three wavelengths. The spectral response in graph 2206shows the frequency versus the relative intensity measured by thebiosensor 100. The graph 2202 illustrates the L value obtained from thespectral responses for each of the three wavelengths obtained, e.g.,from the spectral response data shown in graph 2206. The L valueobtained for the three wavelengths is a measured response from thepulsating arterial blood flow in the patient.

The graph 2208 illustrates the calculated Ratio R forR₁=L_(390 nm)/L_(940 nm) and R₂=L_(390 nm)/L_(660 nm). In one aspect,based on unexpected results from clinical trials, it was determined thata ratio R value obtained at approximately L_(λ1)=390 nm and L_(λ2)=940nm is useful as a predictor or indicator of diabetic risk or diabetes.For example, during experimental clinical trials, spectral responseswere obtained during a measurement period over a 1-2 minute time periodfor wavelengths of 390 nm and 940 nm (and also in ranges of 1 nm to 50nm including these wavelengths). An R value was obtained based on thespectral responses. From the unexpected results of the clinical trials,an R value obtained during a period of fasting, e.g. prior to ingestionof food or liquids, of less than 1 (e.g., approximately 0.5) indicatedthat a person has diabetes or early onset of diabetes. An R value of 2or above indicated that a person has a lower risk of a diabetesdiagnosis. An R value in the 5-6 range indicated no current risk ofdiabetes. For example, as shown in graph 2208, the R value obtained forL_(λ1)=390 nm and L_(λ2)=940 nm has an average value greater than 5 inthis first patient without a diabetes diagnosis.

In particular, in unexpected results, it is believed that nitric oxideNO levels in the arterial blood flow is being measured at least in partby the biosensor 100 using the spectral response for the wavelength 390nm (and 1 nm-50 nm range around 390 nm). The spectral response isresponsive to nitric oxide (NO) concentration levels in the blood. Assuch, the L_(390 nm) values may be used to determine nitric oxide (NO)concentration levels in the pulsating blood flow.

In addition, insulin in the blood generates NO as it penetrates bloodvessel walls. The NO is released as a gas before attaching to one ormore hemoglobin type molecules. Since at least part of the NO gasconcentration is in a gaseous form in the arterial blood flow, the NO inthe gaseous form will dissipate prior to measurement from in vitro bloodsamples. As such, the complete NO concentration levels may not bemeasured using in vitro blood samples, e.g. from a finger prick. Thus,the biosensor 100 measurements, e.g. using the spectral response andcalculated L values at 390 nm, are the first time NO levels in arterialblood flow have been measured in vivo. These unexpected results ofmeasuring nitric oxide NO concentration levels in pulsating arterialblood flow are obtained non-invasively and continuously over ameasurement period using the biosensor 100.

From the clinical trials performed, it has been determined that themeasured NO levels are an indication of insulin response and bloodglucose concentration levels in the blood. The R value derived fromL_(390 nm)/L_(940 nm) may thus be used as an indicator of insulinresponse and diabetic risk as well as vascular health. These unexpectedresults have advantages in early detection of diabetic risk and easier,non-invasive monitoring of insulin resistance and blood glucose levels.The biosensor 100 may display the R value or an analysis of the diabeticrisk based on the R value. In one aspect, the biosensor 100 may display,no diabetic risk based on R values of 5 or greater. In another aspect,the biosensor 100 may display, low diabetic risk based on R values of2-5. In another aspect, the biosensor 100 may display, high diabeticrisk based on an R values of 1-2. In another aspect, the biosensor 100may display, diabetic condition detected based on an R value less thanone.

FIG. 23 illustrates a schematic drawing of another exemplary embodimentof results of clinical data 2300 obtained using an embodiment of thebiosensor 100 from a second patient. The second patient is a 59 year oldmale with a known diagnosis of Type 2 diabetes. At predetermined timeperiods of about 15 minutes, blood glucose level (BGL) was measuredusing a known method of a blood glucose meter (BGM) using blood fromfinger pricks. The BGM glucose measurements 2304 are plotted. Theplotted measurements were interpolated to generate a polynomial 2306showing the approximate BGM glucose measurements over time in mG/DLunits. The biosensor 100 obtained measurements over the same time periodto derive the Ratio R for approximately L_(390 nm)/L_(940 nm) 2302, asshown on the graph as well.

In this clinical trial, the base insulin resistance factor 2308 measuredprior to eating has a low baseline value of about 0.5 indicating adiabetic condition. In unexpected results, the base insulin resistancefactor or R value for L_(390 nm)/L_(940 nm) of less than 1 (in an Rvalue range of 0-8) thus seems to indicate a diabetic condition from theclinical trial results. After consumption of a high sugar substance,insulin response 2310 is seen after about 7 minutes. The blood glucoselevels may be obtained from the R values using the graph 2300 or asimilar calibration table that correlates the R value with known BGLmeasurements for the patient. The calibration table may be generated fora specific patient or may be generated from a sample of a generalpopulation. It is determined that the R values should correlate tosimilar BGL measurements across a general population. Thus, thecalibration table may be generated from testing of a sample of a generalpopulation.

From the unexpected results of the clinical trials, an R value of lessthan 1 (in an R value range of 0-8) indicated that a person has diabetesor early onset of diabetes. An R value of 5 (in an R value range of 0-8)or above indicated that a person has no diabetic condition. For example,as shown in graph 2208, the base insulin resistance factor measuredusing an R value of approximately L_(390 nm)/L_(940 nm) has generally anaverage value greater than 5 in the first patient without a diabetesdiagnosis. The base insulin resistance factor measured using an R valueof approximately L_(390 nm)/L_(940 nm) was generally an average valueless than 1 (in an R value range from 0-8) in the other patients with adiabetes diagnosis of either Type 1 or Type II. The base insulinresistance factor measured using an R value in the 1-2 (in an R valuerange from 0-8) range indicated a high risk of diabetes and need forfurther testing.

It seems that the L_(390 nm) is measuring NO levels in the arterialblood flow. As insulin is generated in the body, it reacts with bloodvessels to generate NO gas. The NO gas bonds to hemoglobin and istransported in the blood stream. The NO is thus a good indicator of abase insulin resistance factor after fasting and an insulin responseafter caloric intake.

From the clinical trials, it seems that the NO levels are reflected inthe R values obtained from L_(390 nm)/L_(940 nm). Based on the clinicaltrials and R values obtained in the clinical trials, it is determinedthat a base insulin resistance factor of less than 1 corresponds to anNO concentration level of at least less than 25% of average NO levels.For example, average NO levels are determined by sampling a generalpopulation of persons without diabetes or other health conditionsaffecting NO levels. From the clinical trials, an R value correlating toa base insulin factor of less than 1 indicates that the NO levels are ina range of 25% to 50% less than average NO levels. After fasting, aperson with a diabetic condition will have low NO concentration levelsthat are at least 25% less than average NO levels due to the low levelof insulin in the blood. Thus, an NO concentration level of at leastless than 25% of normal ranges of NO concentration levels indicates adiabetic condition (e.g., the NO levels corresponding to R value lessthan 1 in this clinical trial). Thus, a base insulin resistance factorof less than 1 correlates to at least less than 25% of average NO levelsof a sample population and indicates a diabetic condition.

Based on the clinical trials and R values obtained in the clinicaltrials, it is determined that a base insulin resistance factor in therange of 2-8 corresponds to average NO concentration levels. Thus, abase insulin resistance factor (e.g. in the range of 2-8) correlates toan average NO level of a sample population and little to no diabeticrisk.

Based on these unexpected results, in one aspect, the biosensor 100 maydisplay or transmit, e.g. to a user device or monitoring station, orotherwise output an indicator of the diabetic risk of a patient based onthe R value. For example, the biosensor 100 may output no diabetic riskbased on an obtained R value for a patient of 5 or greater. In anotheraspect, the biosensor 100 may output low diabetic risk based on anobtained R value of 2-5. In another aspect, the biosensor 100 may outputhigh diabetic risk based on an obtained R values of 1-2. In anotheraspect, the bio sensor 100 may output diabetic condition detected basedon an R value less than one. In the clinical trials herein, the R valuewas in a range of 0-8. Other ranges, weights or functions derived usingthe R value described herein may be implemented that changes thenumerical value of the R values described herein or the range of the Rvalues described herein. In general, from the results obtained herein,an R value corresponding to at least the lower 10% of the R value rangeindicates a diabetic condition, an R value in the lower 10% to 25% ofthe R value range indicates a high risk of diabetes, an R value in the25% to 60% range indicates a low risk of diabetes, and an R valuegreater than 60% indicates no diabetic condition.

The R value of L_(390 nm)/L_(940 nm) may be non-invasively and quicklyand easily obtained using the biosensor 100 in a physician's office orother clinical setting or at home. In one aspect, the R value may beused to determine whether further testing for diabetes needs to beperformed. For example, upon detection of a low R value of less than 1,a clinician may then determine to perform further testing andmonitoring, e.g. using glucose ingestion tests over a longer period oftime or using the biosensor 100 over a longer period of time or othertype of testing.

Embodiment—Blood Alcohol Level Measurements

FIG. 24 illustrates a schematic drawing of another exemplary embodimentof results of clinical data 2400 obtained using an embodiment of thebiosensor 100 from a third patient. In this trial, the third patient wasa 55 year old male that ingested a shot of whiskey at approximately 7seconds. The biosensor 100 was used to measure an indicator of bloodalcohol levels over a measurement period of approximately 271 secondsusing a wavelength of approximately 468 nm. The graph illustrates thevalues obtained for ratio R=L_(468 nm)/L_(940 nm) 2802 over themeasurement period. The biosensor 100 was able to detect the increase inthe blood alcohol levels over the measurement period. The ratio R values2802 may be correlated with blood alcohol levels using a table or graphthat associates the R values 2402 with blood alcohol levels. Forexample, the table or graph may be obtained through blood alcohol levelsmeasured from blood drawn at preset intervals (such as every 1-5minutes) during a measurement period (such as 1-5 hours) andinterpolating the resulting measurements. The interpolated measurementsare then associated with the measured ratio R values 2402 over the samemeasurement period. In general, the ratio R values 2402 are consistentwith an approximate measured blood alcohol level in subsequent clinicaltrials for a patient. The calibration of measured blood alcohol levelsto ratio R values 2402 may thus only be performed once for a patient. Inanother aspect, the calibration table may be generated using testing ofa sample of a general population. It is determined that the R valuesshould correlate to similar BAL measurements across a generalpopulation. Thus, the calibration table may be generated from testing ofa sample of a general population.

In unexpected results, concentration levels of a liver enzyme calledcytochrome P450 Oxidase (P450) that is generated in the presence ofalcohol may be measured by the biosensor 100. The spectral responsearound the wavelength at approximately 468 nm seems to track theconcentration levels of the liver enzyme P450. The liver enzyme isgenerated to react with various substances and may be generated inresponse to alcohol levels. Thus, the measurement of the spectralresponse for the wavelength at approximately 468 nm may indicate bloodalcohol levels and/or concentration levels of P450.

Embodiment—Digestive Stage and Caloric Intake Measurements

FIG. 25 illustrates a schematic drawing of another exemplary embodimentof results of clinical data 2500 obtained using the biosensor 100 from afourth patient. In this trial, the fourth patient ingested whiskey atapproximately 13 seconds. The biosensor 100 was used to measure thedigestive stages over a measurement period of approximately 37 minutesusing a wavelength of approximately 390 nm to track the blood glucoselevels. The graph illustrates the values for L_(390 nm) 2502 obtainedover the measurement period. The biosensor 100 was able to detect thedigestive stage 1 2504 and digestive stage 2 2506 based on the obtainedvalues for L_(390 nm). The first digestive stage 1 2504 is indicated byan initial spike around 20 seconds as blood rushes to the stomach to aidin digestion. The second digestive stage 2 is indicated by a later, moreprolonged increase in blood glucose levels between 60 and 180 seconds.

Based on the insulin response and BGL measurements, a calibration ofcaloric intake may be performed for a patient. For example, knowncaloric intakes may be correlated with insulin response in phase 1 andphase 2 digestions measured using values for L_(390 nm) 2502. In anotheraspect, the calibration table may be generated using testing of a sampleof a general population. It is determined that the R values usingL_(390 nm) 2502 should correlate to similar caloric intake measurementsacross a general population. Thus, the calibration table may begenerated from testing of a sample of a general population.

Embodiment—Liver Enzyme Measurements

In unexpected results, concentration levels of a liver enzyme calledcytochrome P450 Oxidase (P450) 2600 was measured by the biosensor 100.In one aspect, spectral response around a wavelength at approximately468 nm was used by the biosensor 100 to obtain L values that tracked theconcentration levels of the liver enzyme P450 2600. The liver enzyme isgenerated to react with various substances 2602 and may be generated inresponse to alcohol levels. Thus, the measurement of the spectralresponse for the wavelength at approximately 468 nm may indicate bloodalcohol levels and/or concentration levels of P450 2600.

Embodiment—Measurements of Other Substances

Using similar principles described herein, the biosensor 100 may measureconcentration levels or indicators of other substances in pulsatingblood flow. For example, using the process 1500 described with respectto FIG. 15, absorption coefficients for one or more frequencies thathave an intensity level responsive to concentration level of substancemay be determined. The biosensor 100 may then detect the substance atthe determined one or more frequencies as described herein and determinethe concentration levels using the Beer-Lambert principles and theabsorption coefficients. The L values and R values may be calculatedbased on the obtained spectral response. In one aspect, the biosensor100 may detect various electrolyte concentration levels or blood analytelevels, such as bilirubin (using L_(460 nm)) and iron (using L_(510 nm),L_(651 nm), L_(300 nm)) and potassium (using L_(550 nm)).

In another aspect, the biosensor 100 may detect sodium chloride NACL(using L_(450 nm)) concentration levels in the arterial blood flow anddetermine determine dehydration level. The biosensor 100 may then outputa determination of level of dehydration based on the detected NACLconcentration levels.

In yet another aspect, the biosensor 100 may be configured to detectproteins or abnormal cells or other elements or compounds associatedwith cancer. The biosensor 100 may measure concentration levels orindicators of other substances in pulsating blood flow using similarprinciples described herein.

For example, the value L_(λ1) is determined from a spectral response ofa wavelength with a high absorption coefficient for the targetedsubstance. The value L_(λ2) is determined from a spectral response ofthe wavelength with a low absorption coefficient for the targetedsubstance. The ratio R_(λ1, λ2) is determined from the value L_(λ1) andthe value L_(λ2). A calibration table may be generated using testing ofa sample of a general population that correlates values of the ratioR_(λ1, λ2) to concentration levels of the target substance. Then theconcentration level of the targeted substance may be determined usingthe calibration table and the measured values for the ratio R_(λ1,λ2).

Embodiment—White Blood Cell Levels and Detection of Infection

The biosensor 100 may detect white blood cell levels and determine apresence of an infection. For example, the biosensor 100 may detect thevarious types of white blood cells based on the spectral response of thewavelengths, e.g. using one or more wavelengths shown in Table 1 below.

TABLE 1 Detection of White Blood Cells White Blood Cell Spectral TypeDiameter Color Absorption Wavelengths Neutrophil 10-12 um Pink - Red,Red - 660 nm Blue, White Blue - 470 nm Green - 580 nm Eosinophil 10-12um Pink 660 nm, 470 nm, 580 nm Orange 600 nm Basophil 12-15 um Blue 470nm Lymphocyte  7-15 um 633 nm Monocyte 15-30 um 580 nm

The biosensor 100 may detect a color or color change of the blood due toan increase or decrease in white blood cells using one or morewavelengths described in Table 1. Based on the detected color or colorchange of the blood, the biosensor 100 may output an alert to a presenceof an infection. For example, the biosensor 100 monitors the color ofthe blood. When it detects a color change indicating an increase inwhite blood cells, the biosensor determines whether this color changemeets a predetermined threshold indicating a presence of an infection.The predetermined threshold may include a color scale and/or length oftime of color change. When the color change reaches the predeterminedthreshold, the biosensor 100 transmits or displays an alert to indicatea presence of an infection.

In another aspect, the biosensor 100 may detect white blood cells fromspectral responses at one or more wavelengths. Due to the larger size ofthe white blood cells from red blood cells, the presence of white bloodcells in the blood affects the spectral width and shape of a spectralresponse.

FIG. 26 illustrates an exemplary graph 2600 of spectral responses of aplurality of wavelengths from clinical data using the biosensor 100. Inthis embodiment, the spectral response of a plurality of wavelengths wasmeasured using the biosensor 100 over a measurement period of almost 600seconds or approximately 10 minutes. The graph illustrates the L valuescalculated from the spectral response for a first wavelength 1402 ofapproximately 940 nm, the spectral response for a second wavelength 1404of approximately 660 nm and the spectral response for a third wavelength1406 of approximately 390 nm obtained from a first biosensor 100measuring reflected light from a first fingertip of a patient. The graphfurther illustrates the spectral response for a fourth wavelength 1410of approximately 592 nm and a fifth wavelength 1412 of approximately 468nm and the spectral response 1408 again at 940 nm obtained from a secondbiosensor measuring reflected light from a second fingertip of apatient. The spectral responses are temporally aligned using thesystolic and diastolic points. Though two biosensors were used to obtainthe spectral responses in this clinical trial, a single biosensor 100may also be configured to obtain the spectral responses of the pluralityof wavelengths.

Due to the size of the white blood cells, the presence of white bloodcells in the blood affects the spectral width and shape of a spectralresponse at one or more wavelengths. In one aspect, from L values 2620shown for the spectral response at 660 nm 2604, the width and shape ofthe spectral response is affected by the presence of white blood cells.For example, the width and shape of L660 nm between 250 and 270 secondshas a different shape and width of L66 nm between 300 and 320 seconds inthe graph 2600. The differences in the width and shape of the spectralresponse may be used to determine a concentration level of white bloodcells or change in concentration level of white blood cells in theblood.

For example, neutrophil levels increase in the presence of an infection.The neutrophil particles have a different color and size from red bloodcells. The biosensor 100 may determine an increase in concentration ofneutrophil in response to a change in color of the blood or change inthe pattern of the spectral response (L value and/or R value) due tochange in size of particles in the blood or a combination of both achange in color and change in a pattern of the spectral response (Lvalue and/or R value).

FIG. 27 illustrates a logical flow diagram of an embodiment of a method2700 to determine a presence of an infection by the biosensor 100. Thebiosensor 100 measures a color or color change of the blood using one ormore wavelengths at 2702. The biosensor 100 may also determine aspectral pattern (e.g. from L values or R values) using one or morewavelengths. The biosensor 100 is configured to compare the color and/orspectral pattern to one or more predetermined thresholds indicating apresence of an infection at 2704. The one or more predeterminedthresholds may include a color scale, spectral patterns and/or length oftime of color change or level of white blood cells detected. Forexample, the biosensor 100 may correlate the determined spectralpatterns with one or more known spectral patterns indicating presence ofwhite blood cells. In another example, the biosensor 100 may compare themeasured color hue, shade or intensity of the blood with known colorhues, shades, or intensities indicating a presence of an infection. Whenthe biosensor 100 detects the biosensor data meets the one or morepredetermined thresholds, the biosensor 100 determines a presence ofinfection at 2708. The biosensor 100 is configured to transmit ordisplay an alert to indicate a presence of the infection at 2710.

Embodiment—Detection of Sleep Apnea

In another aspect, the biosensor 100 may detect sleep apnea. Thebiosensor 100 is configured to determine periods of sleep of thepatient. The determination may be based on input from the activitymonitoring circuit 114, measured respiration rates, heart rate, etc. Thebiosensor 100 monitors and tracks the oxygen saturation levels SpO₂during the periods of sleep. The biosensor 100 may compare the measuredpattern of the oxygen saturation levels during sleep with known patternsassociated with sleep apnea. Based on this comparison, the biosensor 100may determine a sleep apnea diagnosis or a high or low risk of sleepapnea for a patient.

Embodiment—Functions Through Health Care Management Chain

FIG. 28 illustrates a schematic block diagram of an embodiment of amethod 2800 for using the biosensor 100 throughout the health caremanagement of a patient. The unique patient identification and biosensordata obtained by the biosensor 100 may be used in one or moreapplications or systems in the health care management of a patient. Aplurality of these functions may be performed concurrently as well asother functions and processes described herein.

At 2802, prior to or at admission, the biosensor 100 is activated for apatient and programmed with a unique patient identification foridentifying the patient. The unique patient identification number isprogrammed into the memory of the biosensor 100 and is associated withthe patient and the EMR of the patient. For example, the biosensor 100may be assigned to a patient upon entry to an emergency room atcheck-in. The biosensor 100 may begin tracking the patient's vitals andother biosensor data prior to a first assessment by a healthcareprovider. Thus, a patient's condition may be monitored and alertsgenerated while a patient is waiting for assessment by physician orother health care provider in an emergency room. The physician or otherhealth care provider will then have a record of the patient's vitals andother biosensor data obtained by the biosensor 100 at the assessment.

At 2804, the biosensor 100 wirelessly communicates the patientidentification with biosensor data to one or more devices for trackingand monitoring of the patient and storing the biosensor data to thepatient's EMR. The biosensor 100 may be used to identify the patientwithout a need for a scanner. The biosensor 100 may also be used fortracking a location of patient in the health care facility based on thewireless communications to one or more local devices. The biosensor 100may be used to track wait times in an emergency room, time and length ofprocedures, medication times and dosages, procedures performed, etc.

At 2806, the biosensor 100 may be used for managing the care of thepatient. For example, the biosensor data 100 may be used to scheduleand/or store physician consultations, physician diagnosis, projecteddischarge dates, recommended discharge orders, treatment options, etc.

At 2810, the biosensor 100 may be used for analyzing the biosensor data.In one aspect, the biosensor 100 or other device may analyze thebiosensor data to determine efficacy of treatment. For example, thebiosensor data may be analyzed to determine whether the condition of thepatient improved over the course of treatment or to determine thetreatments with more positive or negative results. The biosensor datamay be analyzed to determine genetic predispositions or conditions. Thebiosensor data may be analyzed to determine diagnosis of conditions andtreatment options.

At 2810, the biosensor 100 is configured for monitoring of patienthealth as described herein. The biosensor 100 is configured to monitorpatient's vitals, determine concentration of one or more substances inthe blood, and perform other monitoring operations described. Thebiosensor data obtained by the biosensor 100 is transmitted with theunique patient identification for monitoring by a remote monitoringstation or storage in the patient EMR. The patient identification storedby the biosensor 100 is wirelessly communicated to one or more localdevices to record administration of medication, performance ofprocedures, etc. Thus, the biosensor 100 continuously and non-invasivelymonitors the health of the patient. The biosensor 100 may replace theneed to measure the patient's vitals with a vitals cart and for drawingblood to determine concentrations of substances in the blood. Thebiosensor 100 also replaces scanning of the barcode on an arm band toidentify a patient. The biosensor 100 also replaces the need to manuallyinput vitals by a health care provider.

At 2812, the biosensor 100 may also transmit wirelessly or reportinformation to an inventory management system. For example, when amedication is provided to a patient, this information of the medicationand dosage may be reported to the inventory management system. Inanother example, when medical supplies are provided to a patient, themedical supplies may include an RFID tag or other identifier that issensed or obtained by the biosensor 100. The biosensor 100 transmits theidentification of the medical supply and the patient identification tothe inventory management system. The inventory management system is thenable to adjust the inventory of the medical supply. The biosensor 100may thus report information on usage of medication or other medicalsupplies for a patient to the inventory management system. Similarinformation may be reported to a billing system for invoicing to thepatient.

The biosensor 100 and health care band 50 provide for continuousmonitoring of a patient's vitals without need for additionalinstruments, manual intervention or disturbing a patient's sleep. Thebiosensor 100 may also be used to perform a blood panel analysis basedon in vivo arterial blood flow without need for invasive blood samplesfrom a patient. The biosensor 100 wirelessly communicates the biosensordata and associated patient identification for monitoring and storage inthe patient's EMR. Thus, a separate scanner for identifying the patientand vitals cart or other additional instrumentation is not always neededto monitor the health of the patient.

Though the above description includes details with respect to pulsatingarterial blood flow, the biosensor 100 may use similar techniquesdescribed herein for pulsating venous blood flow. The biosensor 100 ispositioned on skin tissue over veins, such as on the wrist, and spectralresponses obtained from light reflected by or transmitted through thepulsating venous blood flow.

One or more embodiments have been described herein for the non-invasiveand continuous biosensor 100. Due to its compact form factor, thebiosensor 100 may be configured for measurements on various skinsurfaces of a patient, including on a forehead, arm, wrist, abdominalarea, chest, leg, ear lobe, finger, toe, ear canal, etc. The biosensorincludes one or more sensors for detecting biosensor data, such as apatient's vitals, activity levels, or concentrations of substances inthe blood flow of the patient. In particular, the PPG sensor isconfigured to monitor concentration levels or indicators of one or moresubstances in the blood flow of the patient. In one aspect, the PPGsensor may non-invasively and continuously detect diabetic parameters,such as insulin resistance, insulin response over time, nitric oxide(NO) levels, glucose levels, and predict diabetic risk or diabeticprecursors, in pulsatile arterial blood flow. In another aspect, the PPGsensor may measure vascular health using NO concentration levels. Inanother aspect, the PPG sensor may detect blood alcohol levels inpulsatile arterial blood flow. In another aspect, the PPG sensor maydetect cytochrome P450 proteins or one or more other liver enzymes orproteins. In another aspect, the PPG sensor may detect digestiveparameters, such as digestion phase 1 and 2 responses. The PPG sensormay detect various electrolyte concentration levels or blood analytelevels, such as bilirubin and sodium and potassium. For example, the PPGsensor may detect sodium NACL concentration levels in the arterial bloodflow to determine dehydration. In yet another aspect, the PPG sensor maybe configured to help diagnose cancer by detecting proteins or abnormalcells or other elements or compounds associated with cancer. In anotheraspect, the PPG sensor may detect white blood cell counts.

In one or more aspects herein, a processing module or circuit includesat least one processing device, such as a microprocessor,micro-controller, digital signal processor, microcomputer, centralprocessing unit, field programmable gate array, programmable logicdevice, state machine, logic circuitry, analog circuitry, digitalcircuitry, and/or any device that manipulates signals (analog and/ordigital) based on hard coding of the circuitry and/or operationalinstructions. A memory is a non-transitory memory device and may be aninternal memory or an external memory, and the memory may be a singlememory device or a plurality of memory devices. The memory may be aread-only memory, random access memory, volatile memory, non-volatilememory, static memory, dynamic memory, flash memory, cache memory,and/or any non-transitory memory device that stores digital information.

As may be used herein, the term “operable to” or “configurable to”indicates that an element includes one or more of circuits,instructions, modules, data, input(s), output(s), etc., to perform oneor more of the described or necessary corresponding functions and mayfurther include inferred coupling to one or more other items to performthe described or necessary corresponding functions. As may also be usedherein, the term(s) “coupled”, “coupled to”, “connected to” and/or“connecting” or “interconnecting” includes direct connection or linkbetween nodes/devices and/or indirect connection between nodes/devicesvia an intervening item (e.g., an item includes, but is not limited to,a component, an element, a circuit, a module, a node, device, networkelement, etc.). As may further be used herein, inferred connections(i.e., where one element is connected to another element by inference)includes direct and indirect connection between two items in the samemanner as “connected to”.

As may be used herein, the terms “substantially” and “approximately”provides an industry-accepted tolerance for its corresponding termand/or relativity between items. Such an industry-accepted toleranceranges from less than one percent to fifty percent and corresponds to,but is not limited to, frequencies, wavelengths, component values,integrated circuit process variations, temperature variations, rise andfall times, and/or thermal noise. Such relativity between items rangesfrom a difference of a few percent to magnitude differences.

Note that the aspects of the present disclosure may be described hereinas a process that is depicted as a schematic, a flowchart, a flowdiagram, a structure diagram, or a block diagram. Although a flowchartmay describe the operations as a sequential process, many of theoperations can be performed in parallel or concurrently. In addition,the order of the operations may be re-arranged. A process is terminatedwhen its operations are completed. A process may correspond to a method,a function, a procedure, a subroutine, a subprogram, etc. When a processcorresponds to a function, its termination corresponds to a return ofthe function to the calling function or the main function.

The various features of the disclosure described herein can beimplemented in different systems and devices without departing from thedisclosure. It should be noted that the foregoing aspects of thedisclosure are merely examples and are not to be construed as limitingthe disclosure. The description of the aspects of the present disclosureis intended to be illustrative, and not to limit the scope of theclaims. As such, the present teachings can be readily applied to othertypes of apparatuses and many alternatives, modifications, andvariations will be apparent to those skilled in the art.

In the foregoing specification, certain representative aspects of theinvention have been described with reference to specific examples.Various modifications and changes may be made, however, withoutdeparting from the scope of the present invention as set forth in theclaims. The specification and figures are illustrative, rather thanrestrictive, and modifications are intended to be included within thescope of the present invention. Accordingly, the scope of the inventionshould be determined by the claims and their legal equivalents ratherthan by merely the examples described. For example, the componentsand/or elements recited in any apparatus claims may be assembled orotherwise operationally configured in a variety of permutations and areaccordingly not limited to the specific configuration recited in theclaims.

Furthermore, certain benefits, other advantages and solutions toproblems have been described above with regard to particularembodiments; however, any benefit, advantage, solution to a problem, orany element that may cause any particular benefit, advantage, orsolution to occur or to become more pronounced are not to be construedas critical, required, or essential features or components of any or allthe claims.

As used herein, the terms “comprise,” “comprises,” “comprising,”“having,” “including,” “includes” or any variation thereof, are intendedto reference a nonexclusive inclusion, such that a process, method,article, composition or apparatus that comprises a list of elements doesnot include only those elements recited, but may also include otherelements not expressly listed or inherent to such process, method,article, composition, or apparatus. Other combinations and/ormodifications of the above-described structures, arrangements,applications, proportions, elements, materials, or components used inthe practice of the present invention, in addition to those notspecifically recited, may be varied or otherwise particularly adapted tospecific environments, manufacturing specifications, design parameters,or other operating requirements without departing from the generalprinciples of the same.

Moreover, reference to an element in the singular is not intended tomean “one and only one” unless specifically so stated, but rather “oneor more.” Unless specifically stated otherwise, the term “some” refersto one or more. All structural and functional equivalents to theelements of the various aspects described throughout this disclosurethat are known or later come to be known to those of ordinary skill inthe art are expressly incorporated herein by reference and are intendedto be encompassed by the claims. Moreover, nothing disclosed herein isintended to be dedicated to the public regardless of whether suchdisclosure is explicitly recited in the claims. No claim element isintended to be construed under the provisions of 35 U.S.C. § 112(f) as a“means-plus-function” type element, unless the element is expresslyrecited using the phrase “means for” or, in the case of a method claim,the element is recited using the phrase “step for.”

The invention claimed is:
 1. A health care band configured forattachment to a patient, comprising: a biosensor attached to the healthcare band, wherein the biosensor includes: a memory configured to storea unique patient identification; a temperature sensor configured toobtain a skin temperature of the patient; a photoplethysmography (PPG)circuit configured to: obtain a plurality of spectral responses at aplurality of wavelengths from light reflected from skin of the patient;determine a concentration level of nitric oxide (NO) in pulsatile bloodflow of the patient using PPG techniques from at least one of theplurality of spectral responses, wherein the at least one of theplurality of spectral responses is obtained at a wavelength with a highabsorption coefficient for NO; and determine biosensor data of thepatient using at least another one of the plurality of spectralresponses, wherein the biosensor data includes oxygen saturation levels,hemoglobin levels or heart rate; and a wireless transceiver configuredto transmit the skin temperature, biosensor data, the NO concentrationlevel and the unique patient identification to one or more remotedevices.
 2. The health care band of claim 1, wherein the PPG circuit isfurther configured to emit light at the plurality of wavelengthsdirected at skin of the patient.
 3. The health care band of claim 1,wherein the PPG circuit is further configured to determine aconcentration level of one or more additional substances using one ormore of the spectral responses.
 4. The health care band of claim 3,wherein the one or more additional substances includes one or more of: ablood alcohol level, a liver enzyme level, a cancer indicating protein,a sodium chloride level, a potassium level, a bilirubin level, and aniron level.
 5. The health care band of claim 1, wherein the biosensorfurther includes an attachment mechanism for detachment and attachmentto the health care band.
 6. The health care band of claim 1, wherein thehealth care band includes a printed bar code, wherein the unique patientidentification is encoded in the printed bar code.
 7. The health careband of claim 1, wherein at least one of the one or more remote devicesis configured to record the temperature, biosensor data, the NOconcentration level and the unique patient identification in anelectronic medical record associated with the unique patientidentification.
 8. The health care band of claim 1, wherein the PPGcircuit is further configured to: detect one or more of the temperature,oxygen saturation level, heart rate or NO concentration level hasreached a predetermined threshold; and generate a medical alert fortransmission by the wireless transceiver to the one or more remotedevices.
 9. The health care band of claim 1, wherein the wirelesstransceiver is configured to transmit the temperature, biosensor data,the NO concentration level and the unique patient identification to oneor more remote devices in a health care facility at periodic intervalsor in response to a request from the one or more remote devices.
 10. Thehealth care band of claim 2, wherein the PPG circuit is furtherconfigured to: determine a presence of an infection by one or more of:comparing one or more of the plurality of spectral responses to one ormore known spectral patterns indicating presence of white blood cells;or determining a color or color change of blood from one or more of theplurality of spectral responses.
 11. The health care band of claim 2,wherein the PPG circuit is further configured to: determine a positionof the biosensor on a skin of a patient, wherein the position includesat least one of: a wrist, an arm, a leg, a finger, a forehead, anearlobe, an ear canal, a forehead, an abdomen, or a chest; and adjust aplurality of frequencies of the emitting light directed at the upperepidermal layer of skin of the patient in response to the position ofthe biosensor.
 12. A biosensor configured for attachment to a patient,comprising: a memory configured to store a unique patientidentification; a PPG circuit configured for obtaining a concentrationlevel of nitric oxide (NO) in pulsatile blood flow of the patient usingPPG techniques, wherein the PPG circuit is configured to: generate atleast a first spectral response for light reflected around a firstwavelength from skin tissue of the patient, wherein the first wavelengthhas a high absorption coefficient for nitric oxide (NO) levels in bloodflow; generate at least a second spectral response for light detectedaround a second wavelength reflected from the skin tissue of thepatient, wherein the second wavelength has a low absorption coefficientfor nitric oxide (NO) in blood flow; a processing circuit configured to:process the first and second spectral responses at the first wavelengthand the second wavelength; and determine a concentration level of NO inthe blood flow of the patient using the first spectral response and thesecond spectral response; and a wireless transceiver configured totransmit the concentration level of NO and the unique patientidentification to one or more devices in a health care facility network.13. The biosensor of claim 12, wherein the processing circuit isconfigured to: determine a glucose concentration level in blood flowusing the concentration level of NO by accessing a calibration tablethat includes a plurality of glucose concentration levels correlatedwith a plurality of concentration levels of NO.
 14. The biosensor ofclaim 12, wherein wireless transceiver is further configured to:transmit the glucose concentration level and the unique patientidentification to an EMR application server for recording in anelectronic medical record associated with the unique patientidentification.
 15. The biosensor of claim 12, wherein the PPG circuitis further configured to: determine a concentration level of one or moreadditional substances including one or more of: a blood alcohol level,hemoglobin levels, a liver enzyme level, a cancer indicating protein, asodium chloride level, a potassium level, a bilirubin level, an ironlevel or a white blood cell level.
 16. The biosensor of claim 12,wherein the biosensor is configured for attachment to a patient on anarm, a wrist, a leg, a finger, a forehead, an earlobe or ear canal. 17.The biosensor of claim 12, wherein the biosensor is further configuredto: determine a position of the biosensor; and adjust operation of thePPG circuit in response to the position of the biosensor.
 18. Thebiosensor of claim 17, wherein the processing circuit is configured todetermine a position of the biosensor by: determining a spectralresponse of underlying tissue from the PPG circuit; determining one ormore characteristics of the underlying tissue from the spectralresponse; correlating the detected one or more characteristics of theunderlying tissue with predetermined characteristics of underlyingtissue from a plurality of body areas, wherein the plurality of bodyparts include at least: an abdominal area, wrist, forearm, leg, finger,earlobe or ear canal; and determining the at least one area of the bodyof the patient on which the biosensor is located based on thecorrelation.
 19. The biosensor of claim 17, wherein the biosensor isconfigured to adjust the operation of the PPG circuit in response to theposition of the biosensor by: adjusting the first wavelength of lightemitted onto the skin of the patient.
 20. The biosensor of claim 17,wherein the biosensor is configured to adjust the operation of the PPGcircuit in response to the position of the biosensor by: adjusting anabsorption coefficient when determining a concentration level of asubstance in response to the underlying tissue.
 21. A biosensorcomprising: a memory configured to store a unique patientidentification; a PPG circuit configured to: obtain a plurality ofspectral responses at a plurality of wavelengths from light reflectedfrom skin of the patient; determine a concentration level of nitricoxide (NO) in blood flow of the patient from at least one of theplurality of spectral responses obtained at a wavelength with a highabsorption coefficient for NO; and determine biosensor data of thepatient using another one of the plurality of spectral responses,wherein the biosensor data includes oxygen saturation levels, hemoglobinlevels or heart rate; and a wireless transceiver configured to transmitthe biosensor data, the NO concentration level and the unique patientidentification to one or more devices in an electronic medical record(EMR) network.
 22. The biosensor of claim 21, further comprising: atemperature sensor configured to detect a temperature of the patient;and an activity monitoring circuit configured to detect an activitylevel of the patient.
 23. The biosensor of claim 22, further comprisinga processing circuit, wherein the processing circuit is furtherconfigured to: track the biosensor data, the NO concentration level andthe unique patient identification and transmit the biosensor data, theNO concentration level and the unique patient identification at periodicintervals to the EMR network.
 24. The biosensor of claim 23, wherein theprocessing circuit is further configured to: associate the uniquepatient identification at an admission stage; and initiate monitoring ofthe biosensor data and the NO concentration level.
 25. The biosensor ofclaim 24, wherein the processing circuit is further configured to:monitor the biosensor data and the NO concentration level of the patientduring an admission period of the health care facility; and periodicallytransmit the biosensor data, the NO concentration level and the uniquepatient identification of the patient at periodic intervals to the EMRnetwork during the admission period of the health care facility.
 26. Thebiosensor of claim 25, wherein the processing circuit is furtherconfigured to: monitor the biosensor data and the NO concentration levelof the patient during one or more medical procedures; and periodicallytransmit the biosensor data, the NO concentration level and the uniquepatient identification of the patient at periodic intervals during theone or more medical procedures to the EMR network.
 27. The biosensor ofclaim 25, wherein the processing circuit is further configured to:analyze the biosensor data and the NO concentration level during theadmission period of the health care facility of the patient to trackefficacy of one or more treatments.